Glucoamylase variants

ABSTRACT

The present invention relates to glucoamylase variants. In particular, the invention relates to variants in the starch binding domain (SBD) of a glucoamylase. The invention also relates to variants having altered properties (e.g., improved thermostability and/or increased specific activity) as compared to a corresponding parent glucoamylase. The present invention also provides enzyme compositions comprising the variant glucoamylases; DNA constructs comprising polynucleotides encoding the variants; and methods of producing the glucoamylase variants in host cells.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to International patent applicationPCT/US07/21683, filed Oct. 9, 2007, which claims priority to U.S.Provisional application 60/850,431, filed Oct. 10, 2006, the contents ofboth are incorporated by reference in their entirety herein.

FIELD OF THE INVENTION

The present invention relates to glucoamylase variants. In particular,the invention relates to variants in the starch binding domain (SBD) ofa glucoamylase. The invention also relates to variants having alteredproperties (e.g., improved thermostability and/or increased specificactivity) as compared to a corresponding parent glucoamylase. Thepresent invention also provides enzyme compositions comprising thevariant glucoamylases; DNA constructs comprising polynucleotidesencoding the variants; and methods of producing the glucoamylasevariants in host cells.

BACKGROUND OF THE INVENTION

Glucoamylase enzymes (glucan 1,4-α-glucohydrolases, EC 3.2.1.3) arestarch hydrolyzing exo-acting carbohydrases, which catalyze the removalof successive glucose units from the non-reducing ends of starch orrelated oligo and polysaccharide molecules. Glucoamylases can hydrolyzeboth the linear and branched glucosidic linkages of starch (e.g.,amylose and amylopectin).

Glucoamylases are produced by numerous strains of bacteria, fungi, yeastand plants. Particularly interesting, and commercially important,glucoamylases are fungal enzymes that are extracellularly produced, forexample from strains of Aspergillus (Svensson et al. (1983) CarlsbergRes. Commun. 48:529-544; Boel et al., (1984) EMBO J. 3:1097-1102;Hayashida et al., (1989) Agric. Biol. Chem. 53:923-929; U.S. Pat. No.5,024,941; U.S. Pat. No. 4,794,175 and WO 88/09795); Talaromyces (U.S.Pat. No. 4,247,637; U.S. Pat. No. 6,255,084 and U.S. Pat. No.6,620,924); Rhizopus (Ashikari et al., (1986) Agric. Biol. Chem.50:957-964; Ashikari et al., (1989) App. Microbiol. and Biotech.32:129-133 and U.S. Pat. No. 4,863,864); Humicola (WO 05/052148 and U.S.Pat. No. 4,618,579) and Mucor (Houghton-Larsen et al., (2003) Appl.Microbiol. Biotechnol. 62:210-217). Many of the genes that code forthese enzymes have been cloned and expressed in yeast, fungal and/orbacterial cells.

Commercially, glucoamylases are very important enzymes and have beenused in a wide variety of applications that require the hydrolysis ofstarch (e.g. for producing glucose and other monosaccharides fromstarch). Glucoamylases are used to produce high fructose cornsweeteners, which comprise over 50% of the sweetener market in theUnited States. In general, glucoamylases may be, and commonly are, usedwith alpha amylases in starch hydrolyzing processes to hydrolyze starchto dextrins and then glucose. The glucose may then be converted tofructose by other enzymes (e.g. glucose isomerases); crystallized; orused in fermentations to produce numerous end products (e.g., ethanol,citric acid, lactic acid, succinate, ascorbic acid intermediates,glutamic acid, glycerol and 1,3-propanediol). Ethanol produced by usingglucoamylases in the fermentation of starch and/or cellulose containingmaterial may be used as a source of fuel or for alcoholic consumption.

Although glucoamylases have been used successfully in commercialapplications for many years, a need still exists for new glucoamylaseswith altered properties, such as improved specific activity andincreased thermostability.

SUMMARY OF THE INVENTION

In one aspect the invention relates to an isolated glucoamylase variantcomprising a catalytic domain and a starch binding domain (SBD), saidSBD comprising one or more amino acid substitutions at a positioncorresponding to position: 493, 494, 495, 501, 502, 503, 508, 511, 517,518, 519, 520, 525, 527, 531, 533, 535, 536, 537, 538, 539, 540, 545,546, 547, 549, 551, 561, 563, 567, 569, 577, 579, and 583 of SEQ ID NO:2 or corresponding to an equivalent position in a parent glucoamylase.In some embodiments, the equivalent position in a parent glucoamylase isdetermined by sequence identity and said parent glucoamylase has atleast 80% amino acid sequence identity and less than 100% amino acidsequence identity with SEQ ID NO:2. In further embodiments, the parentglucoamylase has at least 90% or at least 95% amino acid sequenceidentity to SEQ ID NO:2. In additional embodiments, the equivalentposition is determined by structural identity to SEQ ID NO:2 or SEQ IDNO: 11. In some embodiments, the parent glucoamylase comprises a SBDhaving at least 95% amino acid sequence identity to a SBD selected fromSEQ ID NO: 11, SEQ ID NO:385, SEQ ID NO:386, SEQ ID NO:387, SEQ IDNO:388, or SEQ ID NO:389. In other embodiments, the catalytic domain hasat least 90% amino acid sequence identity to the sequence of SEQ IDNO:3. In yet other embodiments, the one or more amino acid substitutionscorrespond to position 520, 535 or 539 of SEQ ID NO:2. In still otherembodiments, the one or more amino acid substitutions correspond toposition 519 and/or 563 of SEQ ID NO:2. In still another embodiment, theisolated glucoamylase variant further comprises one or more amino acidsubstitutions at a position corresponding to residue position: 10, 14,15, 23, 42, 45, 46, 59, 60, 61, 67, 68, 72, 73, 97, 98, 99, 102, 108,110, 113, 114, 122, 124, 125, 133, 140, 144, 145, 147, 152, 153, 164,175, 182, 204, 205, 214, 216, 219, 228, 229, 230, 231, 236, 239, 240,241, 242, 244, 263, 264, 265, 268, 269, 276, 284, 291, 300, 301, 303,310, 311, 313, 316, 338, 342, 344, 346, 349, 359, 361, 364, 379, 382,390, 391, 393, 394, 408, 410, 415, 417, 418, 430, 431, 433, 436, 442,443, 444, 448 and 451 of SEQ ID NO: 2 or SEQ ID NO: 3.

In another aspect the invention relates to an isolated glucoamylasevariant comprising a catalytic domain and a SBD, said SBD comprising oneor more amino acid substitutions at a position corresponding toposition: 493, 494, 495, 502, 503, 508, 511, 518, 519, 520, 527, 531,535, 536, 537, 539, 563, and 577 of SEQ ID NO: 2 or corresponding to anequivalent position in a parent glucoamylase. In some embodiments, theparent glucoamylase has at least 90% sequence identity to SEQ ID NO: 2.In further embodiments, the one or more amino acid substitutionscorresponds to: T493C, T493M, T493N, T493Q, T493Y, P494H, P494I, P494M,P494N, P494Q, P494W, T495M, T495P, T495R, H502A, H502M, H502S, H502V,E503C, E503D, E503H, E503S, E503W, Q508N, Q508P, Q508Y, Q511C, Q511G,Q511H, Q511, Q51K, Q51T, Q511V, N518P, N518T, A519I, A520C, A520E,A520L, A520P, A520Q, A520R, A520W, V531A, V5311L, V531N, V531R, V531S,V531T, A535E, A535F, A535G, A535K, A535L, A535N, A535P, A535R, A535S,A535T, A535V, A535W, A535Y, V536C, V536E, V536I V536L, V536M, V536Q,V536S, A539E, A539M, A539R, A539S, and A539W of SEQ ID NO: 2 or anequivalent position in a parent glucoamylase. In further embodiments,the one or more amino acid substitutions correspond to position T495R,E503C, E503S, Q511H, V531L, or V536I of SEQ ID NO:2. In yet furtherembodiments, the one or more amino acid substitutions correspond topositions 494, 511, 520, 527, 531, 535, 536, 537, 563 and 577 of SEQ IDNO:2.

In other aspects the invention relates to a glucoamylase variantcomprising a catalytic domain and a SBD, said SBD comprising one or moreamino acid substitutions at a position corresponding to position: T493I,T495K, T495R, T495S, E503A, E503C, E503S, E503T, E503V, Q508H, Q508R,Q508S, Q508T, Q511A, Q511D, Q511H, Q511N, Q511S, N518S, A519E, A519K,A519R, A519T, A519V, A519Y, A520C, A520L, A520P, T527A, T527V, V531L,A535D, A535K, A535N, A535P, A535R, V536I, V536R, N537W, A539E, A539H,A539M, A539R, A539S, N563A, N563C, N563E, N5631, N563K, N563L, N563Q,N563T, N563V, N577A, N577K, N577P, N577R, and N577V of SEQ ID NO: 2 oran equivalent position in a parent glucoamylase. In some embodiments,the parent glucoamylase has at least 90% sequence of SEQ ID NO:2.

In yet other aspects the invention relates to a glucoamylase variantcomprising a catalytic domain and a SBD, said SBD comprising one or moreamino acid substitutions at a position corresponding to position 503,511, 519, 531, 535, 539, 563, and 577 of SEQ ID NO: 2. In someembodiments, the one or more amino acid substitutions is chosen fromE503A, E503C, E503V, Q511H, A519K, A519R, A519Y, V531L, A535K, A535N,A535P, A535R, A539E, A539R, A539S, N563C, N563E, N5631, N563K, N563L,N563Q, N563T, N563V, N577K, N577P, and N577R of SEQ ID NO:2.

In another aspect the invention relates to a glucoamylase variantcomprising a catalytic domain and a starch binding domain (SBD), a) saidcatalytic domain comprising at least 85% sequence identity to the aminoacid sequence of SEQ ID NO:3 and b) said SBD comprising one or moreamino acid substitutions at a position corresponding to position: 3, 4,5, 11, 12, 13, 18, 21, 27, 28, 29, 30, 35, 37, 41, 43, 45, 46, 47, 48,49, 50, 55, 56, 57, 59, 61, 71, 73, 77, 79, 87, 89, and 93 of SEQ ID NO:11 or said SBD comprising one or more amino acid substitutions in anequivalent position to SEQ ID NO: 11 of a parent glucoamylase SBD. Insome embodiments, the catalytic domain has at least 90% sequenceidentity to the amino acid sequence of SEQ ID NO:3. In furtherembodiments, the catalytic domain has at least 95% sequence identity tothe amino acid sequence of SEQ ID NO:3. In additional embodiments, theSBD comprises one or more amino acid substitutions at a positioncorresponding to position: 3, 4, 5, 11, 12, 13, 18, 21, 27, 28, 29, 30,35, 37, 41, 43, 45, 46, 47, 48, 49, 50, 55, 56, 57, 59, 61, 71, 73, 77,79, 87, 89, and 93 of SEQ ID NO: 11. In other embodiments, the SBDcomprises one or more amino acid substitutions corresponding topositions 3, 4, 5, 12, 13, 18, 21, 28, 29, 30, 37, 41, 45, 46, 47, 49,73, and 87 of SEQ ID NO: 11 or an equivalent position of a SBD of aparent glucoamylase. In yet other embodiments, the one or more aminoacid substitutions correspond to position 3, 5, 13, 18, 21, 28, 29, 30,37, 41, 45, 46, 47, 49, 73, and 87 of SEQ ID NO: 11. In still otherembodiments, the one or more amino acid substitutions correspond to aposition chosen from positions 5, 13, 21, 30, 41, 45, 46, and 49 of SEQID NO: 11.

In additional aspects of the invention, the glucoamylase variant willhave at least one altered property compared to a corresponding parentglucoamylase. In some embodiments, the altered property is an increasedspecific activity. In further embodiments, the altered property is anincreased thermostability. In additional embodiments, the alteredproperty is both increased specific activity and increasedthermostability.

In still further aspects of the invention, the parent glucoamylase ischosen from a glucoamylase obtained from a Trichoderma spp., anAspergillus spp., a Humicola spp., a Penicillium spp., a Talaromycesspp, or a Schizosaccharmyces spp. In some embodiments, the parentglucoamylase comprises the sequence of SEQ ID NOs: 2, 3, 4, 5, 6, 7, 8,or 9.

Other aspects of the invention include polynucleotides encoding theglucoamylase variants encompassed by the invention and host cellscomprising the polynucleotides.

Further aspects of the invention include enzyme compositions comprisingthe glucoamylase variant encompassed by the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A illustrates a Trichoderma reesei glucoamylase (TrGA) having 632amino acids (SEQ ID NO: 1). The signal peptide is underlined, thecatalytic region (SEQ ID NO:3) starting with amino acid residues SVDDFI(SEQ ID NO: 12) and having 453 amino acid residues is in bold; thelinker region is in italics and the starch binding domain (SBD) is bothitalics and underlined. The mature protein which includes the catalyticdomain (SEQ ID NO:3), linker region (SEQ ID NO:10) and starch bindingdomain (SEQ ID NO:11) is represented by SEQ ID NO:2. With respect to theSBD numbering of the TrGA glucoamylase molecule, reference is made inthe present disclosure to either a) positions 491 to 599 in SEQ ID NO:2of the mature TrGA and/or positions 1 to 109 in SEQ ID NO: 11 whichrepresents the isolated SBD sequence of the mature TrGA. With respect tothe catalytic domain numbering of the TrGA molecule reference is made toSEQ ID NO: 2 and SEQ ID NO: 3.

FIG. 1B illustrates the cDNA (SEQ ID NO:4) which codes for the TrGA.FIG. 1C illustrates the precursor and mature protein TrGA domains.

FIG. 2 illustrates the destination plasmid pDONR-TrGA which includes thecDNA (SEQ ID NO:4) of the TrGA.

FIG. 3 illustrates the plasmid pTTT-Dest.

FIG. 4 illustrates the final expression vector pTTT-TrGA.

FIGS. 5A-5B illustrate an alignment comparison of the catalytic domainsof parent glucoamylases including glucoamylases derived from Aspergillusawamori (AaGA) (SEQ ID NO:5); Aspergillus niger (AnGA) (SEQ ID NO:6);Aspergillus oryzae (AoGA) (SEQ ID NO:7); Trichoderma reesei (TrGA) (SEQID NO:3); Humicola grisea (HgGA) (SEQ ID NO:8); and Hypocrea vinosa(HvGA) (SEQ ID NO:9). Identical amino acids are indicated by an asterisk(*).

FIG. 5C illustrates a Talaromyces glucoamylase (TeGA) mature proteinsequence (SEQ ID NO:384).

FIGS. 5D-5E illustrates an alignment comparing the Starch Binding Domain(SBD) of parent glucoamylases including Trichoderma reesei (SEQ ID NO:11), Humicola grisea (HgGA) (SEQ ID NO:385), Thermomyces lanuginosus(ThGA) (SEQ ID NO:386), Talaromyces emersonii (TeGA) (SEQ ID NO:387),Aspergillus niger (AnGA) (SEQ ID NO:388); and Aspergillus awamori (AaGA)(SEQ ID NO:389).

FIG. 6 is a comparison of the three dimensional structures ofTrichoderma glucoamylase (black) (SEQ ID NO:2) and Aspergillus awamoriglucoamylase (grey) viewed from the side. The side is measured inreference to the active site. For example, in FIGS. 6-8 the active siteentrance is defined as the “top” of the molecule.

FIG. 7 is a comparison of the three dimensional structures ofTrichoderma glucoamylase (black) and Aspergillus awamori glucoamylase(grey) viewed from the top.

FIG. 8 is an alignment of the three dimensional structures of TrGA(black) and A. niger GA (gray) viewed from the side showing binding site1 and 2.

FIG. 9 is a model of the binding of acarbose to the TrGA crystalstructure shown in FIG. 6.

DETAILED DESCRIPTION OF THE INVENTION I. Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Singleton, et al., DICTIONARYOF MICROBIOLOGY AND MOLECULAR BIOLOGY, 2D ED., John Wiley and Sons, NewYork (1994), and Hale & Markham, THE HARPER COLLINS DICTIONARY OFBIOLOGY, Harper Perennial, N.Y. (1991) provide one of skill with thegeneral meaning of many of the terms used herein. Still, certain termsare defined below for the sake of clarity and ease of reference.

As used herein, the term “glucoamylase (EC 3.2.1.3)” refers to an enzymethat catalyzes the release of D-glucose from the non-reducing ends ofstarch and related oligo- and polysaccharides.

The term “parent” or “parent sequence” refers to a native or naturallyoccurring sequence or reference sequence having sequence and/orstructural identity with TrGA (SEQ ID NOs:1 and/or 2).

The term “TrGA” refers to a parent Trichoderma reesei glucoamylasesequence having the mature protein sequence illustrated in SEQ ID NO:2which includes the catalytic domain having the sequence illustrated inSEQ ID NO:3. The isolation, cloning and expression of the TrGA aredescribed in WO 2006/060062 and U.S. Pat. Pub. No. 2006/0094080published May 4, 2006 which are incorporated herein by reference. TheTrGA is also considered a parent glucoamylase sequence. In someembodiments, the parent sequence refers to a TrGA that is the startingpoint for protein engineering.

The phrase “mature form of a protein or polypeptide” refers to the finalfunctional form of the protein or polypeptide. To exemplify, a matureform of the TrGA includes the catalytic domain, linker region and starchbinding domain having the amino acid sequence of SEQ ID NO:2.

The term “Trichoderma glucoamylase homologues” refers to parentglucoamylases having at least at least 50% sequence identity, at least60% sequence identity, at least 70% sequence identity, at least 80%amino acid sequence identity to the TrGA sequence (SEQ ID NO:2) andwhich glucoamylases retain the functional characteristics of aglucoamylase.

As used herein, a “homologous sequence” means a nucleic acid orpolypeptide sequence having at least 100%, at least 99%, at least 98%,at least 97%, at least 96%, at least 95%, at least 94%, at least 93%, atleast 92%, at least 91%, at least 90%, at least 88%, at least 85%, atleast 80%, at least 75%, at least 70%, at least 65%, at least 60%, atleast 55%, at least 50%, or at least 45% sequence identity to a nucleicacid sequence or polypeptide sequence when optimally aligned forcomparison, wherein the function of the candidate nucleic acid sequenceor polypeptide sequence is essentially the same as the nucleic acidsequence or polypeptide sequence said candidate homologous sequence isbeing compared with. In some embodiments, homologous sequences havebetween 85% and 100% sequence identity, while in other embodiments thereis between 90% and 100% sequence identity, and in other embodiments,there is 95% and 100% sequence identity. In some embodiments thecandidate homologous sequence (e.g. reference sequence) or parent iscompared with the TrGA nucleic acid sequence or mature protein sequence.The sequence identity can be measured over the entire length of theparent or homologous sequence.

As used herein, the terms “glucoamylase variant”, “SBD variant” and“TrGA variant” are used in reference to glucoamylases that are similarto a parent or reference glucoamylase sequence (e.g., the TrGA orTrichoderma glucoamylase homologues) but have at least one substitution,deletion or insertion in the amino acid sequence of the SBD that makesthem different in sequence from a parent or reference glucoamylase.

As used herein the term “catalytic domain” refers to a structural regionof a polypeptide, which contains the active site for substratehydrolysis.

The term “linker” refers to a short amino acid sequence generally havingbetween 3 and 40 amino acids residues that covalently bind an amino acidsequence comprising a starch binding domain with an amino acid sequencecomprising a catalytic domain.

The term “starch binding domain (SBD)” refers to an amino acid sequencethat binds preferentially to a starch substrate.

As used herein, the terms “mutant sequence” and “mutant gene” are usedinterchangeably and refer to a polynucleotide sequence that has analteration in at least one codon occurring in a host cell's parentsequence. The expression product of the mutant sequence is a variantprotein with an altered amino acid sequence relative to the parent. Theexpression product may have an altered functional capacity (e.g.,enhanced enzymatic activity).

The term “property” or grammatical equivalents thereof in the context ofa polypeptide, as used herein, refers to any characteristic or attributeof a polypeptide that can be selected or detected. These propertiesinclude, but are not limited to oxidative stability, substratespecificity, catalytic activity, thermal stability, pH activity profile,resistance to proteolytic degradation, K_(M), K_(CAT), K_(CAT)/K_(M)ratio, protein folding, ability to bind a substrate and ability to besecreted.

The term “property” or grammatical equivalent thereof in the context ofa nucleic acid, as used herein, refers to any characteristic orattribute of a nucleic acid that can be selected or detected. Theseproperties include, but are not limited to, a property affecting genetranscription (e.g., promoter strength or promoter recognition), aproperty affecting RNA processing (e.g., RNA splicing and RNAstability), a property affecting translation (e.g., regulation, bindingof mRNA to ribosomal proteins).

The term “specific activity” is defined as the activity per mg of activeglucoamylase protein. Activity is determined using the ethanol assay asdescribed herein. A variant identified as having a Performance Index(PI)>1.0 compared to the parent TrGA PI is considered as having anincreased specific activity. PI is calculated from the specificactivities (activity/mg enzyme) of the parent (WT) and the variantglucoamylase. It is the quotient “variant-specific activity/WT-specificactivity”.

The terms “thermally stable” and “thermostable” refer to glucoamylasevariants of the present invention that retain a specified amount ofenzymatic activity after exposure to identified temperatures over agiven period of time under conditions prevailing during the hydrolysisof starch substrates, for example while exposed to altered temperatures.

The term “enhanced stability” in the context of a property such asthermostability refers to a higher retained starch hydrolytic activityover time as compared to another reference glucoamylase (e.g., parentglucoamylase).

The term “diminished stability” in the context of a property such asthermostability refers to a lower retained starch hydrolytic activityover time as compared to other glucoamylases, variants and/or wild-typeglucoamylase.

The terms “active” and “biologically active” refer to a biologicalactivity associated with a particular protein. It follows that thebiological activity of a given protein refers to any biological activitytypically attributed to that protein by those skilled in the art. Forexample, an enzymatic activity associated with a glucoamylase ishydrolytic and, thus an active glucoamylase has hydrolytic activity.

The terms “polynucleotide” and “nucleic acid”, used interchangeablyherein, refer to a polymeric form of nucleotides of any length, eitherribonucleotides or deoxyribonucleotides. These terms include, but arenot limited to, a single-, double- or triple-stranded DNA, genomic DNA,cDNA, RNA, DNA-RNA hybrid, or a polymer comprising purine and pyrimidinebases, or other natural, chemically, biochemically modified, non-naturalor derivatized nucleotide bases.

As used herein, the terms “DNA construct,” “transforming DNA” and“expression vector” are used interchangeably to refer to DNA used tointroduce sequences into a host cell or organism. The DNA may begenerated in vitro by PCR or any other suitable technique(s) known tothose in the art. The DNA construct, transforming DNA or recombinantexpression cassette can be incorporated into a plasmid, chromosome,mitochondrial DNA, plastid DNA, virus, or nucleic acid fragment.Typically, the recombinant expression cassette portion of an expressionvector, DNA construct or transforming DNA includes, among othersequences, a nucleic acid sequence to be transcribed and a promoter. Insome embodiments, expression vectors have the ability to incorporate andexpress heterologous DNA fragments in a host cell.

As used herein, the term “vector” refers to a polynucleotide constructdesigned to introduce nucleic acids into one or more cell types. Vectorsinclude cloning vectors, expression vectors, shuttle vectors, plasmids,cassettes and the like.

As used herein in the context of introducing a nucleic acid sequenceinto a cell, the term “introduced” refers to any method suitable fortransferring the nucleic acid sequence into the cell. Such methods forintroduction include but are not limited to protoplast fusion,transfection, transformation, conjugation, and transduction.

As used herein, the terms “transformed” and “stably transformed” referto a cell that has a non-native (heterologous) polynucleotide sequenceintegrated into its genome or as an episomal plasmid that is maintainedfor at least two generations.

As used herein, the terms “selectable marker” and “selective marker”refer to a nucleic acid (e.g., a gene) capable of expression in hostcells which allows for ease of selection of those hosts containing thevector. Typically, selectable markers are genes that conferantimicrobial resistance or a metabolic advantage on the host cell toallow cells containing the exogenous DNA to be distinguished from cellsthat have not received any exogenous sequence during the transformation.

As used herein, the term “promoter” refers to a nucleic acid sequencethat functions to direct transcription of a downstream gene. Thepromoter, together with other transcriptional and translationalregulatory nucleic acid sequences (also termed “control sequences”) isnecessary to express a given gene. In general, the transcriptional andtranslational regulatory sequences include, but are not limited to,promoter sequences, ribosomal binding sites, transcriptional start andstop sequences, translational start and stop sequences, and enhancer oractivator sequences.

A nucleic acid is “operably linked” when it is placed into a functionalrelationship with another nucleic acid sequence. For example, DNAencoding a secretory leader (i.e., a signal peptide), is operably linkedto DNA for a polypeptide if it is expressed as a preprotein thatparticipates in the secretion of the polypeptide. Generally, “operablylinked” means that the DNA sequences being linked are contiguous, and,in the case of a secretory leader, contiguous and in reading phase.

As used herein the term “gene” refers to a polynucleotide (e.g., a DNAsegment), that encodes a polypeptide and includes regions preceding andfollowing the coding regions as well as intervening sequences (introns)between individual coding segments (exons).

As used herein, “homologous genes” refers to a pair of genes fromdifferent, but usually related species, which correspond to each otherand which are identical or very similar to each other. The termencompasses genes that are separated by speciation (i.e., thedevelopment of new species) (e.g., orthologous genes), as well as genesthat have been separated by genetic duplication (e.g., paralogousgenes).

As used herein, “ortholog” and “orthologous genes” refer to genes indifferent species that have evolved from a common ancestral gene (i.e.,a homologous gene) by speciation. Typically, orthologs retain the samefunction during the course of evolution. Identification of orthologsfinds use in the reliable prediction of gene function in newly sequencedgenomes.

As used herein, “paralog” and “paralogous genes” refer to genes that arerelated by duplication within a genome. While orthologs retain the samefunction through the course of evolution, paralogs evolve new functions,even though some functions are often related to the original one.Examples of paralogous genes include, but are not limited to genesencoding trypsin, chymotrypsin, elastase, and thrombin, which are allserine proteinases and occur together within the same species.

As used herein, “homology” refers to sequence similarity or identity,with identity being preferred. This homology is determined usingstandard techniques known in the art (See e.g., Smith and Waterman, Adv.Appl. Math., 2:482 [1981]; Needleman and Wunsch, J. Mol. Biol., 48:443[1970]; Pearson and Lipman, Proc. Natl. Acad. Sci. USA 85:2444 [1988];programs such as GAP, BESTFIT, FASTA, and TFASTA in the WisconsinGenetics Software Package (Genetics Computer Group, Madison, Wis.); andDevereux et al., Nucl. Acid Res., 12:387-395 [1984]).

The “percent (%) nucleic acid sequence identity” or “percent (%) aminoacid sequence identity” is defined as the percentage of nucleotideresidues or amino acid residues in a candidate sequence that areidentical with the nucleotide residues or amino acid residues of thestarting sequence (i.e., TrGA).

Homologous sequences are determined by known methods of sequencealignment. A commonly used alignment method is BLAST described byAltschul et al., (Altschul et al., (1990) J. Mol. Biol., 215:403-410;and Karlin et al., (1993) Proc. Natl. Acad. Sci. USA 90:5873-5787). Aparticularly useful BLAST program is the WU-BLAST-2 program (See,Altschul et al., (1996) Meth. Enzymol., 266:460-480). WU-BLAST-2 usesseveral search parameters, most of which are set to the default values.The adjustable parameters are set with the following values: overlapspan=1, overlap fraction=0.125, word threshold (T)=11. The HSP S and HSPS2 parameters are dynamic values and are established by the programitself depending upon the composition of the particular sequence andcomposition of the particular database against which the sequence ofinterest is being searched. However, the values may be adjusted toincrease sensitivity. A % amino acid sequence identity value isdetermined by the number of matching identical residues divided by thetotal number of residues of the “longer” sequence in the aligned region.The “longer” sequence is the one having the most actual residues in thealigned region (gaps introduced by WU-Blast-2 to maximize the alignmentscore are ignored).

Other methods find use in aligning sequences. One example of a usefulalgorithm is PILEUP. PILEUP creates a multiple sequence alignment from agroup of related sequences using progressive, pairwise alignments. Itcan also plot a tree showing the clustering relationships used to createthe alignment. PILEUP uses a simplification of the progressive alignmentmethod of Feng and Doolittle (Feng and Doolittle, J. Mol. Evol.,35:351-360 [1987]). The method is similar to that described by Higginsand Sharp (Higgins and Sharp, CABIOS 5:151-153 [1989]). Useful PILEUPparameters including a default gap weight of 3.00, a default gap lengthWeight of 0.10, and weighted end gaps.

The term “optimal alignment” refers to the alignment giving the highestpercent identity score.

An “equivalent position” refers to an alignment between two sequenceswherein the alignment is optimal. For example using FIGS. 5D and 5E,position 491 in TrGA (SEQ ID NO: 2) is C491; the equivalent position forAspergillus niger is position C509; and the equivalent position forAspergillus awamori is position Q538. See FIG. 8 for an exemplaryalignment of the three-dimensional sequence.

As used herein, the term “hybridization” refers to the process by whicha strand of nucleic acid joins with a complementary strand through basepairing, as known in the art.

A nucleic acid sequence is considered to be “selectively hybridizable”to a reference nucleic acid sequence if the two sequences specificallyhybridize to one another under moderate to high stringency hybridizationand wash conditions. Hybridization conditions are based on the meltingtemperature (Tm) of the nucleic acid binding complex or probe. Forexample, “maximum stringency” typically occurs at about Tm −5° C. (5°below the Tm of the probe); “high stringency” at about 5-10° C. belowthe Tm; “intermediate stringency” at about 10-20° C. below the Tm of theprobe; and “low stringency” at about 20-25° C. below the Tm.Functionally, maximum stringency conditions may be used to identifysequences having strict identity or near-strict identity with thehybridization probe; while an intermediate or low stringencyhybridization can be used to identify or detect polynucleotide sequencehomologs.

Moderate and high stringency hybridization conditions are well known inthe art. An example of high stringency conditions includes hybridizationat about 42° C. in 50% formamide, 5×SSC, 5×Denhardt's solution, 0.5% SDSand 100 μg/ml denatured carrier DNA followed by washing two times in2×SSC and 0.5% SDS at room temperature and two additional times in0.1×SSC and 0.5% SDS at 42° C. An example of moderate stringentconditions include an overnight incubation at 37° C. in a solutioncomprising 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate),50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextransulfate and 20 mg/ml denatured sheared salmon sperm DNA, followed bywashing the filters in 1×SSC at about 37-50° C. Those of skill in theart know how to adjust the temperature, ionic strength, etc. asnecessary to accommodate factors such as probe length and the like.

As used herein, “recombinant” includes reference to a cell or vector,that has been modified by the introduction of a heterologous orhomologous nucleic acid sequence or that the cell is derived from a cellso modified. Thus, for example, recombinant cells express genes that arenot found in identical form within the native (non-recombinant) form ofthe cell or express native genes that are otherwise abnormallyexpressed, under expressed or not expressed at all as a result ofdeliberate human intervention.

In some embodiments of the invention, mutated DNA sequences aregenerated with site saturation mutagenesis in at least one codon. Inanother embodiment, site saturation mutagenesis is performed for two ormore codons. In a further embodiment, mutant DNA sequences have morethan 50%, more than 55%, more than 60%, more than 65%, more than 70%,more than 75%, more than 80%, more than 85%, more than 90%, more than95%, more than 98%, or more than 99% homology with the parent sequence.In alternative embodiments, mutant DNA is generated in vivo using anyknown mutagenic procedure such as, for example, radiation,nitrosoguanidine and the like. The desired DNA sequence is then isolatedand used in the methods provided herein.

As used herein, “heterologous protein” refers to a protein orpolypeptide that does not naturally occur in the host cell.

As used herein, “homologous protein” refers to a protein or polypeptidenative or naturally occurring in a cell and includes native proteinsthat are over-expressed in the cell whether by recombinant DNAtechnology or naturally.

An enzyme is “over-expressed” in a host cell if the enzyme is expressedin the cell at a higher level than the level at which it is expressed ina corresponding wild-type cell.

The terms “protein” and “polypeptide” are used interchangeably herein.In the present disclosure and claims, the conventional one-letter andthree-letter codes for amino acid residues are used. The 3-letter codefor amino acids as defined in conformity with the IUPAC-IUB JointCommission on Biochemical Nomenclature (JCBN). It is also understoodthat a polypeptide may be coded for by more than one nucleotide sequencedue to the degeneracy of the genetic code.

Variants of the invention are described by the following nomenclature:[original amino acid residue/position/substituted amino acid residue].For example the substitution of leucine for arginine at position 76 isrepresented as R76L. When more than one amino acid is substituted at agiven position, the substitution is represented as 1) Q172C, Q172D orQ172R; 2) Q172C, D, or R or c) Q172C/D/R. When a position suitable forsubstitution is identified herein without a specific amino acidsuggested, it is to be understood that any amino acid residue may besubstituted for the amino acid residue present in the position. Where avariant glucoamylase contains a deletion in comparison with otherglucoamylases the deletion is indicated with “*”. For example, adeletion at position R76 is represented as R76′. A deletion of two ormore consecutive amino acids is indicated for example as (76-78)*.

A “prosequence” is an amino acid sequence between the signal sequenceand mature protein that is necessary for the secretion of the protein.Cleavage of the pro sequence will result in a mature active protein.

The term “signal sequence” or “signal peptide” refers to any sequence ofnucleotides and/or amino acids which may participate in the secretion ofthe mature or precursor forms of the protein. This definition of signalsequence is a functional one, meant to include all those amino acidsequences encoded by the N-terminal portion of the protein gene, whichparticipate in the effectuation of the secretion of protein. They areoften, but not universally, bound to the N-terminal portion of a proteinor to the N-terminal portion of a precursor protein. The signal sequencemay be endogenous or exogenous. The signal sequence may be that normallyassociated with the protein (e.g., glucoamylase), or may be from a geneencoding another secreted protein.

The term “precursor” form of a protein or peptide refers to a matureform of the protein having a prosequence operably linked to the amino orcarbonyl terminus of the protein. The precursor may also have a “signal”sequence operably linked, to the amino terminus of the prosequence. Theprecursor may also have additional polypeptides that are involved inpost-translational activity (e.g., polypeptides cleaved therefrom toleave the mature form of a protein or peptide).

“Host strain” or “host cell” refers to a suitable host for an expressionvector comprising DNA according to the present invention.

The terms “derived from” and “obtained from” refer to not only aglucoamylase produced or producible by a strain of the organism inquestion, but also a glucoamylase encoded by a DNA sequence isolatedfrom such strain and produced in a host organism containing such DNAsequence. Additionally, the term refers to a glucoamylase which isencoded by a DNA sequence of synthetic and/or cDNA origin and which hasthe identifying characteristics of the glucoamylase in question.

A “derivative” within the scope of this definition generally retains thecharacteristic hydrolyzing activity observed in the wild-type, native orparent form to the extent that the derivative is useful for similarpurposes as the wild-type, native or parent form. Functional derivativesof glucoamylases encompass naturally occurring, synthetically orrecombinantly produced peptides or peptide fragments which have thegeneral characteristics of the glucoamylases of the present invention.

The term “isolated” or “purified” refers to a material that is removedfrom its original environment (e.g., the natural environment if it isnaturally occurring). In some embodiments, an isolated protein is morethan 10% pure, preferably more than 20% pure, and even more preferablymore than 30% pure, as determined by SDS-PAGE. Further aspects of theinvention encompass the protein in a highly purified form (i.e., morethan 40% pure, more than 60% pure, more than 80% pure, more than 90%pure, more than 95% pure, more than 97% pure, and more than 99% pure) asdetermined by SDS-PAGE.

As used herein, the term, “combinatorial mutagenesis” refers to methodsin which libraries of variants of a starting sequence are generated. Inthese libraries, the variants contain one or several mutations chosenfrom a predefined set of mutations. In addition, the methods providemeans to introduce random mutations which were not members of thepredefined set of mutations. In some embodiments, the methods includethose set forth in U.S. Pat. No. 6,582,914, hereby incorporated byreference. In alternative embodiments, combinatorial mutagenesis methodsencompass commercially available kits (e.g., QuikChange® Multisite,Stratagene, San Diego, Calif.).

As used herein, the term “library of mutants” refers to a population ofcells which are identical in most of their genome but include differenthomologues of one or more genes. Such libraries can be used, forexample, to identify genes or operons with improved traits.

As used herein the term “dry solids content (DS or ds)” refers to thetotal solids of a slurry in % on a dry weight basis.

As used herein, the term “target property” refers to the property of thestarting gene that is to be altered. It is not intended that the presentinvention be limited to any particular target property. However, in someembodiments, the target property is the stability of a gene product(e.g., resistance to denaturation, proteolysis or other degradativefactors), while in other embodiments, the level of production in aproduction host is altered. Indeed, it is contemplated that any propertyof a starting gene will find use in the present invention. Otherdefinitions of terms may appear throughout the specification

Before the exemplary embodiments are described in more detail, it is tobe understood that this invention is not limited to particularembodiments described, as such may, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimits of that range is also specifically disclosed. Each smaller rangebetween any stated value or intervening value in a stated range and anyother stated or intervening value in that stated range is encompassedwithin the invention. The upper and lower limits of these smaller rangesmay independently be included or excluded in the range, and each rangewhere either, neither or both limits are included in the smaller rangesis also encompassed within the invention, subject to any specificallyexcluded limit in the stated range. Where the stated range includes oneor both of the limits, ranges excluding either or both of those includedlimits are also included in the invention.

Although any methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of the presentinvention, exemplary and preferred methods and materials are nowdescribed. All publications mentioned herein are incorporated herein byreference to disclose and describe the methods and/or materials inconnection with which the publications are cited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. Thus, for example, reference to “agene” includes a plurality of such candidate agents and reference to“the cell” includes reference to one or more cells and equivalentsthereof known to those skilled in the art, and so forth.

The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present invention isnot entitled to antedate such publication by virtue of prior invention.

II. Embodiments Parent Glucoamylases:

In some embodiments, the present invention provides a glucoamylasevariant of a parent glucoamylase. The parent glucoamylase comprises acatalytic domain and a starch binding domain. The parent glucoamylasecan comprise a sequence that has sequence and/or structural identitywith TrGA (SEQ ID NO:2). In some embodiments, the parent glucoamylasecomprises an amino acid sequence as illustrated in SEQ ID NO: 1, 2, 5,6, 7, 8, 9 or 384. In some embodiments, the parent glucoamylase is ahomologue. In some embodiments, the parent glucoamylase has at least50%, sequence identity, including at least 60%, at least 70%, at least80%, at least 90%, at least 95%, at least 96%, at least 97%, at least98%, and at least 99% sequence identity with the TrGA amino acidsequence of SEQ ID NO:2.

In some embodiments, the parent glucoamylase comprises a catalyticdomain having an amino acid sequence having at least 50% amino acidsequence identity with one or more of the amino acid sequencesillustrated in SEQ ID NO:1, 2, 3, 5, 6, 7, 8 or 384, including at least60%, at least 70%, at least 80%, at least 90%, at least 95% and at least99% sequence identity to SEQ ID NO:1, 2, 3, 5, 6, 7, 8 and/or 384. Inother embodiments, the parent glucoamylase has at least 80% sequenceidentity, at least 85% sequence identity, at least 90% sequenceidentity, at least 95% sequence identity, at least 97% sequenceidentity, at least 98% sequence identity, and at least 99% sequenceidentity with the catalytic domain of the TrGA amino acid sequence SEQID NO:3.

In some embodiments, the parent glucoamylase comprises a starch bindingdomain having structural identity with SEQ ID NO:11. In someembodiments, the parent glucoamylase comprises a starch binding domainhaving an amino acid sequence having at least 30% sequence identity, atleast 40% sequence identity, at least 50% sequence identity, at least60% sequence identity, at least 70% sequence identity, at least 80%sequence identity, at least 85% sequence identity, at least 90% sequenceidentity, at least 95% sequence identity, at least 97% sequenceidentity, at least 98% sequence identity, and at least 99% sequenceidentity with the SBD of the TrGA amino acid sequence SEQ ID NO:11.

The parent glucoamylase can be encoded by a DNA sequence whichhybridizes under medium, high or stringent conditions with a DNAencoding a glucoamylase comprising one of the amino acid sequences ofSEQ ID NO: 1, 2, and/or 11. In some embodiments, the encodedglucoamylase has at least 50% sequence identity, at least 60% sequenceidentity, at least 70% sequence identity, at least 80% sequenceidentity, at least 85% sequence identity, at least 90% sequenceidentity, at least 95% sequence identity, at least 97% sequenceidentity, at least 98% sequence identity, and at least 99% sequenceidentity with the amino acid sequence SEQ ID NO: 1, 2, and/or 11. Insome embodiments, the parent glucoamylase is a native or naturallyoccurring sequence in a host cell. In some embodiments, the parentglucoamylase is a naturally occurring variant. In some embodiments, theparent glucoamylase is a reference sequence which is a variant that hasbeen engineered or is a hybrid glucoamylase.

Predicted structure and known sequences of glucoamylases are conservedamong fungal species (Coutinho et al., 1994 Protein Eng., 7:393-400 andCoutinho et al., 1994, Protein Eng., 7: 749-760). In some embodiments,the parent glucoamylase is a filamentous fungal glucoamylase. In someembodiments, the parent glucoamylase is obtained from a Trichodermastrain (e.g., T. reesei, T. longibrachiatum, T. strictipilis, T.asperellum, T. konilangbra and T. hazianum), an Aspergillus strain (e.g.A. niger, A. nidulans, A. kawachi, A. awamori and A. orzyae), aTalaromyces strain (e.g. T. emersonii, T. thermophilus, and T. duponti),a Hypocrea strain (e.g. H. gelatinosa, H. orientalis, H. vinosa, and H.citrina), a Fusarium strain (e.g., F. oxysporum, F. roseum, and F.venenatum), a Neurospora strain (e.g., N. crassa) and a Humicola strain(e.g., H. grisea, H. insolens and H. lanuginosa), a Penicillium strain(e.g. P. notatum or P. chrysogenum), or a Saccharomycopsis strain (e.g.S. fibuligera). In some embodiments, the parent glucoamylase comprisesthe amino acid sequence of those sequences illustrated in FIGS. 5A-E.

In some embodiments, the parent glucoamylase may be a bacterialglucoamylase. For example, the glucoamylase may be obtained from a grampositive bacterial strains such as Bacillus (e.g., B. alkalophilus, B.amyloliquefaciens, B. lentus, B. licheniformis, B. stearothermophilus,B. subtilis and B. thuringiensis) or a Streptomyces strain (e.g., S.lividans).

In some embodiments, the parent glucoamylase will have at least 50%sequence identity, at least 60% sequence identity, at least 70% sequenceidentity, at least 80% sequence identity, at least 85% sequenceidentity, at least 88% sequence identity, at least 90% sequenceidentity, at least 93% sequence identity, at least 95% sequenceidentity, at least 96% sequence identity, at least 97% sequenceidentity, at least 98% sequence identity and also at least 99% sequenceidentity with the TrGA amino acid sequence of SEQ ID NO: 2. In someembodiments, the parent glucoamylase also has structural identity to SEQID NO:2.

In further embodiments, a Trichoderma glucoamylase homologue will beobtained from a Trichoderma or Hypocrea strain. Some Trichodermaglucoamylase homologues are described in US Pat. Pub. No. 2006/0094080and reference is made specifically to amino acid sequences set forth inSEQ ID NOs: 17-22 and 43-47 of said reference.

In some embodiments, the parent glucoamylase is TrGA comprising theamino acid sequence of SEQ ID NO:2 or a Trichoderma glucoamylasehomologue having at least 50%, at least 60%, at least 70%, at least 80%,at least 85%, at least 88%, at least 90%, at least 93%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99% sequence identity tothe TrGA sequence. In some embodiments, the parent glucoamylase hasstructural identity to the TrGA sequence (SEQ ID NO:2) and comprises aSBD having structural identity to the TrGA SBD (SEQ ID NO:11).

A parent glucoamylase can be isolated and/or identified using standardrecombinant DNA techniques. Any standard techniques can be used that areknown to the skilled artisan. For example, probes and/or primersspecific for conserved areas of the glucoamylase can be used to identifyhomologues in bacterial or fungal cells (the catalytic domain, theactive site, etc.). Alternatively degenerate PCR can be used to identifyhomologues in bacterial or fungal cells. In some cases, known sequences,such as in a database, can be analyzed for sequence and/or structuralidentity to one of the known glucoamylases, including SEQ ID NO: 2 or aknown starch binding domain, including SEQ ID NO: 11. Functional assayscan also be used to identify glucoamylase activity in a bacterial orfungal cell. Proteins having glucoamylase activity can be isolated andreverse sequenced to isolate the corresponding DNA sequence. Suchmethods are known to the skilled artisan.

Glucoamylase Structural Homology:

The central dogma of molecular biology is that the sequence of DNAencoding a gene for a particular enzyme, determines the amino acidsequence of the protein, this sequence in turn determines thethree-dimensional folding of the enzyme. This folding brings togetherdisparate residues that create a catalytic center and substrate bindingsurface and this results in the high specificity and activity of theenzymes in question.

Glucoamylases consist of as many as three distinct structural domains, acatalytic domain of approximately 450 residues which is structurallyconserved in glucoamylases, generally followed by a linker regionconsisting of between 30 and 80 residues which are connected to a starchbinding domain of approximately 100 residues. The structure of theTrichoderma reesei glucoamylase with all three regions intact wasdetermined to 1.8 Angstrom resolution herein (see Table 8 and Example11). Using the coordinates (see Table 8) the catalytic structure wasaligned with the coordinates of the catalytic domain from Aspergillusawamori strain X100 that was determined previously (Aleshin, A. E.,Hoffman, C., Firsov, L. M., and Honzatko, R. B. 1994 Refined crystalstructures of glucoamylase from Aspergillus awamori var. X100. J MolBiol 238: 575-591.). The Aspergillus awamori crystal structure onlyincluded the catalytic domain. As seen in FIGS. 6 and 7 the structure ofthe catalytic domains overlap very closely and it is possible toidentify equivalent residues based on this structural superposition. Theinventors believe that glucoamylases share the basic structure depictedin FIGS. 6 and 7.

FIGS. 6 and 7 are comparisons of the three dimensional structures of theTrichoderma glucoamylase (black) of SEQ ID NO:1 (see FIG. 1 for aminoacid sequence) and of Aspergillus awamori (grey) viewed from the sideand top, respectively. The side is defined in relationship to the activesite of the molecule which is at the “top.” In the side view therelationship between the catalytic domain and the linker region and thestarch binding domain can be seen. The glucoamylases shown here andindeed known glucoamylases to date share this structural homology,particularly in the catalytic domain. The conservation of structure ofthe glucoamylase molecule correlates with the conservation of activityand a conserved mechanism of action for all glucoamylases. Given thishigh homology, site specific variants of the Trichoderma glucoamylaseresulting in altered function would also have similar structural andtherefore functional consequences in other glucoamylases. Therefore, theteachings of which variants result in desirable benefits can be appliedto other glucoamylases.

A further crystal structure was produced using the coordinates in Table8 for the Starch Binding Domain. The SBD for TrGA was aligned with theSBD for A. niger. As shown in FIG. 8 the structure of the A. niger andTrGA SBDs overlaps very closely. The inventors believe that, while allstarch binding domains share at least some of the basic structuredepicted in FIG. 8, some SBDs are more structurally similar than others.For example, the TrGA SBD can be classified as within the carbohydratebinding module 20 family within the CAZY database (cazy.org). The CAZYdatabase describes the families of structurally-related catalytic andcarbohydrate-binding modules (or functional domains) of enzymes thatdegrade, modify or create glycosidic bonds. Given a high structuralhomology, site specific variants of the TrGA SBD resulting in alteredfunction would also have similar structural and therefore functionalconsequences in other glucoamylases having SBDs with similar structureto that of the TrGA SBD, particularly those classified within thecarbohydrate binding module 20 family. Thus, the teachings of whichvariants result in desirable benefits can be applied to other SBDshaving structural similarity.

Structural identity determines whether the amino acid residues areequivalent. Structural identity is a one-to-one topological equivalentwhen the two structures (three dimensional and amino acid structures)are aligned. A residue (amino acid) position of a glucoamylase isequivalent to a residue of T. reesei glucoamylase if it is eitherhomologous (i.e., corresponding in position in either primary ortertiary structure) or analogous to a specific residue or portion ofthat residue in T. reesei glucoamylase (having the same or similarfunctional capacity to combine, react, or interact chemically).

In order to establish identity to the primary structure, the amino acidsequence of a glucoamylase can be directly compared to Trichodermareesei glucoamylase primary sequence and particularly to a set ofresidues known to be invariant in glucoamylases for which sequence isknown. For example, FIGS. 5A and B herein shows the conserved residuesbetween glucoamylase catalytic domains. FIGS. 5D and E show an alignmentof starch binding domains from glucoamylases. After aligning theconserved residues, allowing for necessary insertions and deletions inorder to maintain alignment (i.e. avoiding the elimination of conservedresidues through arbitrary deletion and insertion), the residuesequivalent to particular amino acids in the primary sequence ofTrichoderma reesei glucoamylase are defined. Alignment of conservedresidues can conserve 100% of such residues. However, alignment ofgreater than 75% or as little as 40% of conserved residues is alsoadequate to define equivalent residues. Further, the structural identitycan be used in combination with the sequence identity to identityequivalent residues.

For example, in FIGS. 5A and 5B, glucoamylases from six organisms arealigned to provide the maximum amount of homology between amino acidsequences. A comparison of these sequences shows that there are a numberof conserved residues contained in each sequence as designated by anasterisk. These conserved residues, thus, may be used to define thecorresponding equivalent amino acid residues of Trichoderma reeseiglucoamylase in other glucoamylases such as glucoamylase fromAspergillus niger. FIGS. 5D and 5E show the SBDs from six organismsaligned to identify equivalent residues between them.

Structural identity involves the identification of equivalent residuesbetween the two structures. “Equivalent residues” can be defined bydetermining homology at the level of tertiary structure (structuralidentity) for an enzyme whose tertiary structure has been determined byNMR techniques and/or x-ray crystallography. For x-ray crystallography,equivalent residues are defined as those for which the atomiccoordinates of two or more of the main chain atoms of a particular aminoacid residue of the Trichoderma reesei glucoamylase (N on N, CA on CA, Con C and O on O) are within 0.13 nm and preferably 0.1 nm afteralignment. Alignment is achieved after the best model has been orientedand positioned to give the maximum overlap of atomic coordinates ofnon-hydrogen protein atoms of the glucoamylase in question to theTrichoderma reesei glucoamylase. The best model is the crystallographicmodel giving the lowest R factor for experimental diffraction data atthe highest resolution available.

${R\mspace{14mu} {factor}} = \frac{{\sum_{h}{{{Fo}(h)}}} - {{{Fc}(h)}}}{\sum_{h}{{{Fo}(h)}}}$

Equivalent residues which are functionally analogous to a specificresidue of Trichoderma reesei glucoamylase are defined as those aminoacids of the enzyme which may adopt a conformation such that they eitheralter, modify or contribute to protein structure, substrate binding orcatalysis in a manner defined and attributed to a specific residue ofthe Trichoderma reesei glucoamylase. Further, they are those residues ofthe enzyme (for which a tertiary structure has been obtained by x-raycrystallography) which occupy an analogous position to the extent that,although the main chain atoms of the given residue may not satisfy thecriteria of equivalence on the basis of occupying a homologous position,the atomic coordinates of at least two of the side chain atoms of theresidue lie with 0.13 nm of the corresponding side chain atoms ofTrichoderma reesei glucoamylase. The coordinates of the threedimensional structure of Trichoderma reesei glucoamylase are set forthin Table 8 and can be used as outlined above to determine equivalentresidues on the level of tertiary structure.

SBD Variants:

The variants according to the invention include at least onesubstitution, deletion or insertion in the amino acid sequence of theSBD of a parent glucoamylase. In some embodiments, the SBD variants ofthe invention will have at least 20%, at least 40%, at least 50%, atleast 60%, at least 70%, at least 80%, at least 85%, at least 90%, atleast 95% at least 97%, and also at least 100% of the glucoamylaseactivity as compared to the glucoamylase activity of TrGA (SEQ ID NO:2)when compared under essentially the same conditions.

In some embodiments, the SBD variants according to the invention willcomprise a substitution, deletion or insertion in at least one aminoacid position of the SBD of the parent TrGA (SEQ ID NO:2), or in anequivalent position in the sequence of another parent glucoamylase. Insome embodiments, the parent glucoamylase has at least 50%, at least60%, at least 70%, at least 80%, at least 90% sequence identity to theTrGA sequence, including but not limited to; at least 93% sequenceidentity, at least 95%, at least 97%, and at least 99% sequence identitywith the catalytic domain of TrGA (SEQ ID NO:3). In some embodiments,the parent glucoamylase has at least 50%, at least 60%, at least 70%, atleast 80%, at least 90% sequence identity to the TrGA sequence,including but not limited to; at least 93% sequence identity, at least95%, at least 97%, and at least 99% sequence identity with the matureprotein of TrGA (SEQ ID NO:2). In some embodiments, the parentglucoamylase will have structural identity to the TrGA sequence.

In some embodiments, the SBD variant will comprise a substitution,deletion or insertion and preferably a substitution in the region ofloop 1 (aa 560-570) and/or the region of loop 2 (aa 523-527) of thesequence corresponding to SEQ ID NO: 2. In particular the regionsincluding amino acid residues 558-562 and/or amino acid residues 570-578are regions for substitution.

In other embodiments, the variant according to the invention willcomprise a substitution, deletion or insertion in at least one aminoacid position of a fragment of the SBD of the parent TrGA, wherein thefragment comprises the catalytic domain and at least part of the SBD ofthe TrGA sequence (SEQ ID NO:3) or in an equivalent position in afragment comprising the catalytic domain of a parent glucoamylase, thecatalytic domain having at least 50%, at least 60%, at least 70%, atleast 80% sequence identity, at least 90%, at least 95%, at least 97%,and at least 99% sequence identity to the fragment of the TrGA sequence.In some embodiments, the SBD fragment will comprise at least 40, 50, 60,70, 80, 90, 100, and/or 109 amino acid residues of the SBD (SEQ ID NO:11). In some embodiments, when the parent glucoamylase includes acatalytic domain, linker region and starch binding domain, the fragmentmay include part of the linker region. In some embodiments, the variantwill comprise a substitution, deletion or insertion in the amino acidsequence of a fragment of the TrGA sequence (SEQ ID NO: 2). In someembodiments, the variant will have structural identity with the TrGAsequence (SEQ ID NO: 2).

In some embodiments, the glucoamylase variant will include at least onesubstitution in the amino acid sequence of the SBD of a parent. Infurther embodiments, the variant may have more than one substitution(e.g. two, three or four substitutions).

While the variants can be in any position in the starch binding domainof the mature protein sequence (SEQ ID NO: 2), in some embodiments, aglucoamylase variant comprises one or more substitutions in thefollowing positions in the amino acid sequence set forth in SEQ ID NO:2:493, 494, 495, 501, 502, 503, 508, 511, 517, 518, 519, 520, 525, 527,531, 533, 535, 536, 537, 538, 539, 540, 545, 546, 547, 549, 551, 561,563, 567, 569, 577, 579, and 583 and/or in an equivalent position in aparent glucoamylase. In some embodiments, the glucoamylase variantcomprises one or more amino acid substitutions corresponding to position493, 494, 495, 502, 503, 508, 511, 518, 519, 520, 527, 531, 535, 536,537, 539, 563, and 577 of SEQ ID NO: 2 or an equivalent position in aparent glucoamylase.

In some embodiments, the variant will include at least one substitutionin a position equivalent to a position set forth in SEQ ID NO:2 andparticularly in a position corresponding to T493, P494, T495, H502,E503, Q508, Q511, N518, A519, A520, T527, V531, A535, V536, N537, A539,N563, and N577 of SEQ ID NO:2 or an equivalent position in a parentglucoamylase.

In some embodiments, the parent glucoamylase will have at least 50%sequence identity, at least 80%, at least 85%, at least 90%, at least95%, at least 96%, at least 97% at least 98%, and at least 99% sequenceidentity with SEQ ID NO: 2. In some embodiments the parent glucoamylaseis a Trichoderma glucoamylase homologue.

In further embodiments, the SBD variant of a glucoamylase parentcomprises at least one of the following substitutions in the followingpositions in an amino acid sequence set forth in SEQ ID NO:2:T493C/M/N/Q/Y; P494H/I/M/N/Q/W; T495M/P/R; H502A/M/S/V; E503C/D/H/S/W;Q508N/P/Y; Q511C/G/H/I/K/T/V; N518S/P/T; A519E/I/K/R/T/V/Y;A520C/E/L/P/Q/R/W; T527A/V; V531A/L/N/R/S/T;A535E/F/G/KL/N/P/R/S/T/V/W/Y; V536C/E/I/L/M/Q/R/S; A539E/H/M/R/S/W;N563A/C/E/I/K/L/Q/T/V; N577A/K/P/R/V and/or a substitution in anequivalent position in a parent glucoamylase homologue.

In some embodiments the isolated glucoamylase variant comprises acatalytic domain having at least 85%, at least 90%, at least 95%, atleast 97%, at least 99% amino acid sequence identity to SEQ ID NO:3 anda SBD comprising one or more amino acid substitutions at a positioncorresponding to position: 3, 4, 5, 11, 12, 13, 18, 21, 27, 28, 29, 30,35, 37, 41, 43, 45, 46, 47, 48, 49, 50, 55, 56, 57, 59, 61, 71, 73, 77,79, 87, 89, and 93 of SEQ ID NO: 11 or a SBD comprising one or moreamino acid substitutions in an equivalent position to SEQ ID NO: 11 of aparent glucoamylase SBD.

SBD Variants Further Including a Substitution, Deletion or Insertion inthe Catalytic Domain:

In some embodiments, the glucoamylase variant will also have asubstitution, deletion or insertion in a catalytic domain in addition tothe SBD. In some embodiments, the catalytic domain substitution,deletion or insertion will include any one of the amino acid residuesillustrated in the sequence of SEQ ID NO: 3. In some embodiments, thevariant comprises one of the catalytic domain variants described in thedisclosure herein. In other embodiments, the variant comprises one ofthe catalytic domain variants described in PCT applicationPCT/US07/21683, filed Oct. 9, 2007 (incorporated by reference). In someembodiments, the catalytic domain variation will include more than onesubstitution in the catalytic domain (e.g. two, three or foursubstitutions) as compared to a corresponding parent glucoamylasecatalytic domain.

In some embodiments, the glucoamylase variant having at least onevariation in the SBD also comprises a substitution, deletion orinsertion in at least one amino acid position in a positioncorresponding to the regions of non-conserved amino acids of thecatalytic domain as illustrated in FIGS. 5A and 5B (e.g. amino acidpositions corresponding to those positions which are not designated by“*” in FIGS. 5A and 5B). In some embodiments, the SBD variant alsocomprises a substitution in at least one amino acid position in aposition corresponding to the regions of non-conserved amino acids asillustrated in FIGS. 5A and 5B.

In some embodiments, the SBD variant encompassed by the inventioncomprises one or more substitutions in the following positions in theamino acid sequence set forth in SEQ ID NOs: 2 or 3: 10, 14, 15, 23, 42,45, 46, 59, 60, 61, 67, 68, 72, 73, 97, 98, 99, 102, 108, 110, 113, 114,122, 124, 125, 133, 140, 144, 145, 147, 152, 153, 164, 175, 182, 204,205, 214, 216, 219, 228, 229, 230, 231, 236, 239, 240, 241, 242, 244,263, 264, 265, 268, 269, 276, 284, 291, 300, 301, 303, 310, 311, 313,316, 338, 342, 344, 346, 349, 359, 361, 364, 375, 379, 382, 390, 391,393, 394, 408, 410, 415, 417, 418, 430, 431, 433, 436, 442, 443, 444,448 and 451, and/or in an equivalent position in a parent glucoamylase.In some embodiments, the parent glucoamylase will have at least 50%, atleast 60%, at least 70%, at least 80%, at least 90%, at least 95%, atleast 96%, at least 97% at least 98%, and at least 99% sequence identitywith SEQ ID NO: 2 or SEQ ID NO: 3. In other embodiments, the parentglucoamylase will be a Trichoderma glucoamylase homologue. In someembodiments, the variant will have altered properties as compared to aparent glucoamylase. In some embodiments, the parent glucoamylase willhave structural identity with the glucoamylase of SEQ ID NOs: 2 or 3.

In some embodiments, the SBD glucoamylase variant also comprises one ormore substitutions in the following positions in the catalytic domain inthe amino acid sequence set forth in SEQ ID NO: 2 or 3: T10, L14, N15,P23, T42, P45, D46, F59, K60, N61, T67, E68, A72, G73, S97, L98, A99,S102, K108, E110, L113, K114, R122, Q124, R125, I133, K140, N144, N145,Y147, S152, N153, N164, F175, N182, A204, T205, S214, V216, Q219, W228,V229, S230, S231, D236, I239, N240, T241, N242, G244, N263, L264, G265,A268, G269, D276, V284, S291, P300, A301, A303, Y310, A311, D313, Y316,V338, T342, S344, T346, A349, V359, G361, A364, T375, N379, S382, S390,E391, A393, K394, R408, S410, S415, L417, H418, T430, A431, R433, I436,A442, N443, S444, T448 and S451 and/or an equivalent position in aparent.

In other embodiments, the SBD variant encompassed herein comprises oneor more substitutions in the following positions of the catalytic domainin the amino acid sequence set forth in SEQ ID NO:2 or 3: 10, 14, 15,23, 59, 60, 61, 65, 67, 68, 72, 73, 97, 98, 99, 102, 110, 113, 133, 140,144, 145, 147, 152, 153, 164, 182, 204, 205, 214, 216, 219, 228, 229,230, 231, 236, 239, 241, 242, 263, 264, 265, 268, 269, 276, 284, 291,300, 301, 303, 311, 338, 342, 344, 346, 349, 359, 361, 364, 375, 379,382, 390, 391, 393, 394, 410, 417, 418, 430, 431, 433, 442, 444, 448,and 451 or an equivalent position in a parent glucoamylase. In someembodiments, the variant has one or more substitutions corresponding toone of the following positions: 61, 67, 72, 97, 102, 133, 205, 219, 228,230, 231, 239, 263, 268, 291, 342, 394, 430, 431 and 451 of SEQ ID NO: 2and/or 3. In some embodiments, the substitution at these positions ischosen from: N611, T67M, A72Y, S97N, S102M, I133T, T205Q, Q219S, W228H,W228M, S230F, S230G, S230N, S230R, S231L, I239V, I239Y, N263P, A268C,A268G, A268K, S291A, T342V, K394S, T430K, A431Q, and S451K of SEQ ID NO:2 and/or 3. In some embodiments, the variant has one or moresubstitutions corresponding to one of the following positions: 72, 133,219, 228, 230, 231, 239, 263, 268, and 451 of SEQ ID NO: 2 and/or 3. Insome embodiments, the substitution at these positions is chosen from:A72Y, I133T, Q219S, W228H, W228M, S230R, S230F, S230G, S231L, I239V,N263P, A268C, A268G, and S451K of SEQ ID NO: 2 and/or 3.

In further embodiments, the SBD variant of a glucoamylase parent alsocomprises at least one of the following substitutions in the followingpositions of the catalytic domain in an amino acid sequence set forth inSEQ ID NO:2 or 3: T10D/F/G/K/L/M/P/R/S; L14E/H; N15D/N; P23A/G; F59A/G;K60F/H; N61D/I/L/Q/V/W; R65A/C/G/I/K/M/S/V/Y; T67C/I/K/M/T; E68I/M/W;A72E/G/L/M/Q/R/W/Y; G73C/L/W; S97F/M/N/P/R/S/V/W/Y; L98H/M;A99C/L/M/N/P; S102A/C/I/L/M/N/R/V/W/Y; E110Q/S/W; L113E/N;K114C/D/E/L/M/Q/S/T/V; I133K/R/S/T; K140A/E/F/H/K/L/M/N/Q/R/S/V/W/Y;N144C/D/E/I/K; N145A1C/E/I/K/L/M/Q/R/V/W/Y; Y147A/M/R; S152H/M;N153C/D/K/L/W/Y; N164A/G; N182C/E/K/P/R; A204C/D/G/I/M/Q/T;T205A/D/H/I/K/M/N/P/Q/S/V/W/Y; S214P/T; V216C/G/H/K/N/Y;Q219D/G/H/N/P/S; W228A/F/G/H/I/L/M/Q/S/T/V/Y; V229E/I/M/N/Q;S230C/D/E/F/G/H/I/K/L/N/P/Q/R/T/V/Y; S231C/D/F/L/M/N/Q/R/S/V/Y;D236F/G/L/M/N/P/S/T/V; I239M/Q/S/V/W/Y; T241C/E/H/L/M/P/S/T/V;N242C/F/H/M/T/V/W; N263H/K/P; L264A/C/E/F/L/S; G265E/G/H/I/K/R/T;A268C/D/E/F/G/I/K/L/P/R/T/W; G269E; D276S; V284R/T/V/Y/A/E/F/H/K/N/P/W;P300K/R; A301E/K/L/P/S/W; A303C/D/F/H/I/K/L/N/R/T/V/W/Y; A311N/P/Q/S/Y;V338P/Q/S/Y; T342N/V; S344A/T; T346G/H/M/N/P/Q/Y; A349L/I/K/M/N/Q/R/W;G361H/L/R; A364M/W; T375C/D/E/H/V/W/Y; N379A/C/D/G/I/M/P/S;S382A/N/P/V/V/W; S390A/Y; E391A/E/I/K/L/M/Q/R/V/W/Y;A393E/G/H/I/K/L/M/N/Q/R/S/T/W/Y; K394A/H/K/L/M/Q/R/S/T/V/W; S410E/H/N;L417A/D/E/F/G/I/K/Q/R/S/T/V/W/Y; H418E/M; T430A/E/F/G/H/I/K/M/N/Q/R/V;A431C/E/H/I/L/M/Q/R/S/W/Y; R433A/C/E/F/G/K/L/M/N/S/V/W/Y;I436E/F/G/H/K/P/R/S/T/V/Y; S444M/N/P/Q/R/T/V/W; T448F/G/I/P/Q/T/V; andS451E/H/K/L/Q/T and/or a substitution in an equivalent position in aparent glucoamylase.

In other embodiments, the SBD variant of a glucoamylase parent alsocomprises one or more substitutions in the following positions in thecatalytic domain amino acid sequence set forth in SEQ ID NO:2 or 3: 10,15, 23, 42, 59, 60, 61, 68, 72, 73, 97, 98, 99, 102, 114, 133, 140, 144,147, 152, 153, 164, 182, 204, 205, 214, 216, 228, 229, 230, 231, 236,241, 242, 263, 264, 265, 268, 269, 276, 284, 291, 300, 301, 303, 311,338, 342, 344, 346, 349, 359, 361, 364, 375, 379, 382, 390, 391, 393,394, 410, 417, 430, 431, 433, 436, 442, 443, 444, 448, and 451 or anequivalent position in a parent glucoamylase. In some embodiments, thevariant has one or more substitutions corresponding to one of thefollowing positions: 10, 42, 68, 73, 97, 114, 153, 229, 231, 236, 264,291, 301, 344, 361, 364, 375, 417, and 433 of SEQ ID NO: 2 and/or 3. Insome embodiments, the substitution at these positions is chosen from:T10S, T42V, E68C, E68M, G73F, G73W, K114M, K114T, N153A, N153S, N153V,W228V, D236R, G361D, G361E, G361P, G361Y, A364D, A364E, A364F, A364G,A364K, A365L, A365R, R433c, R433G, R433L, R433N, R433S, R433V, and I436Hof SEQ ID NO: 2 and/or 3. In some embodiments, the variant has one ormore substitutions corresponding to one of the following positions: 42,68, 73, 114, 153, 236, 361, and 364 of SEQ ID NO; 2 and/or 3. In someembodiments, the substitution at these positions is chosen from: T42V,E68M, G73F, G73W, K114T, N153S, N153V, D236R, G361D, A364F, and A364L ofSEQ ID NO: 2 and/or 3.

In some embodiments, the SBD variant has one or more substitutionscorresponding to one of the following positions: 228, 230, 231, 268,291, 417, 433, and 451 of SEQ ID NO: 2 or 3. In some embodiments, thesubstitution at these positions is chosen from: W228H, W228M, S230F,S230G, S230R, S231L, A268C, A268G, S291A, L417R, R433Y, and S451K of SEQID NO: 2 and/or 3.

Chimeric or Hybrid SBD Glucoamylase Variants:

Glucoamylase variants of the invention may also include chimeric orhybrid glucoamylases with, for example a starch binding domain (SBD)from one glucoamylase and a catalytic domain and linker from another.For example, a hybrid glucoamylase can be made by swapping the SBD fromAnGA with the SBD from TrGA, making a hybrid with the AnGA SBD and theTrGA catalytic domain and linker. Alternatively, the SBD and linker fromAnGA can be swapped for the SBD and linker of TrGA. In one embodiment aSBD glucoamylase variant according to the invention will comprise acatalytic domain from an Aspergillus glucoamylase, a Humicolaglucoamylase, a Thermomyces glucoamylase, or a Talaromyces glucoamylaseand a SBD comprising one or more amino acid substitutions at a positioncorresponding to position: 3, 4, 5, 11, 12, 13, 18, 21, 27, 28, 29, 30,35, 37, 41, 43, 45, 46, 47, 48, 49, 50, 55, 56, 57, 59, 61, 71, 73, 77,79, 87, 89, and 93 of SEQ ID NO: 11. In some embodiments, the catalyticdomain may comprise anyone of the following sequences SEQ ID NO:5; SEQID NO:6; SEQ ID NO:7, SEQ ID NO:8 or SEQ ID NO:9.

Altered Properties:

The glucoamylase variants encompassed by the invention may also have atleast one altered property (e.g., improved property) as compared to aparent glucoamylase and particularly compared to the TrGA. In someembodiments, at least one altered property is selected from increased pHstability, increased thermal stability and/or increased specificactivity. In some embodiments, the increased pH stability is at pH7.0-8.5. In further embodiments, the increased pH stability is at pHlevels less than 7.0, less than 6.5, less than 6.0 (such as pH between6.5 and 6.0, between 6.0 and 5.5, between 6.0 and 5.0 and between 6.0and 4.5).

The glucoamylase variants of the invention may also provide higher ratesof starch hydrolysis at low substrate concentrations as compared to theparent glucoamylase. The variant may have a higher Vmax or lower Km thana parent glucoamylase when tested under the same conditions. For examplethe variant glucoamylase may have a higher Vmax at a temperature rangeof 25° C. to 70° C. (e.g. at 25° C. to 35° C.; 30° C.-35° C.; 40° C. to50° C.; at 50° C. to 55° C. and at 55° C. to 62° C.). TheMichaelis-Menten constant, Km and Vmax values can be easily determinedusing standard known procedures.

SBD Variants with Increased Thermostability:

In some embodiments, the variant glucoamylases encompassed by theinvention will have altered thermal stability as compared to a parent(wild type). Thermostability is measured as the % residual activityafter incubation for 1 hour at 64 degree centigrade in NaAc buffer pH4.5. Under these conditions TrGA has a residual activity of betweenabout 15% and 44% due to day-to-day variation as compared to the initialactivity before incubation. Thus, in some embodiments, variants withincreased thermostability have a residual activity that is between atleast 1% and at least 50% more than that of the parent (after incubationfor 1 hour at 64 degrees centigrade in NaAc buffer pH 4.5), including2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%,18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%,32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%,46%, 47%, 48%, 49%, and 50% as compared to the initial activity beforeincubation. For example, when the parent residual activity is 15%, avariant with increased thermal stability may have a residual activity ofbetween about 15% and about 75%. In some embodiments, the glucoamylasevariants of the invention will have improved thermostability such asretaining at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%,97%, 98% or 99% enzymatic activity after exposure to alteredtemperatures over a given time period, for example, at least 60 minutes,120 minutes, 180 minutes, 240 minutes, 300 minutes, etc. In someembodiments, the variant has increased thermal stability compared to theparent glucoamylase at selected temperatures in the range of about 40 toabout 90° C., about 40 to about 85° C., about 45 to about 80° C., about50 to about 75° C., about 60 to about 75° C. and also about 60 to 70° C.In some embodiments, a SBD variant has increased thermostable comparedto a parent glucoamylase at temperatures above 70° C., above 75° C.,above 80° C. and above 85° C. at a pH range of 4.0 to 6.0. In someembodiments, the thermostability is determined as described in theExamples. In some embodiments, the variant has increased stability atlower temperatures compared to the parent glucoamylase such as in therange of 20 to 50° C., including 35 to 45 and 30° C. to 40° C.

In some embodiments, glucoamylase variants encompassed by the inventionhaving increased thermostability include those having one or moresubstitutions in the following positions in the amino acid sequence setforth in SEQ ID NO:2: 493, 495, 503, 508, 511, 518, 519, 520, 527, 531,535, 536, 537, 539, 563, and 577 or an equivalent position in a parentglucoamylase. In some embodiments, the parent glucoamylase will be aTrichoderma glucoamylase homologue and in further embodiments, theparent glucoamylase will have at least 90%, at least 95% and at least98% sequence identity to SEQ ID NO:2. In some embodiments, thesubstitution will be chosen from T493I, T495K/R/S, E503A/C/S/T/V,Q508H/R/S/T, Q511A/D/H/N/S, N518S, A519E/K/R/T/V/Y, A520C/L/P, T527A/V,V531L, A535D/K/N/P/R, V536I/R, N537W, A539E/H/M/R/S,N563A/C/E/I/K/L/Q/T/V, and N577A/K/P/R/V.

In further embodiments, glucoamylase variants encompassed by theinvention having increased thermostability include the SBD variantsdelineated in the paragraph above and additionally include one or moredeletions, substitutions or insertions and particularly substitutions inthe following positions in the amino acid sequence set forth in SEQ IDNO:2 or SEQ ID NO:3: T10, N15, P23, T42, F59, K60, N61, E68, A72, G73,S97, L98, A99, S102, K114, I133, K40, N144, Y147, S 52, N153, N164,N182, A204, T205, S214, V216, W228, V229, S230, S231, D236, T241, N242,N263, L264, G265, A268, G269, D276, V284, S291, P300, A301, A303, A311,V338, T342, S344, T346, A349, V359, G361, A364, T375, N379, S382, S390,E391, A393, K394, S410, L417, T430, A431, R433, I436, A442, N443, S444,T448 and S451 and/or an equivalent position in a parent glucoamylase. Insome embodiments, the parent glucoamylase will be a Trichodermaglucoamylase homologue and in further embodiments, the parentglucoamylase will have at least 50%, at least 60%, at least 70%, atleast 80%, at least 90%, at least 95% and at least 98% sequence identityto SEQ ID NO:2 or SEQ ID NO:3. In some embodiments, the parentglucoamylase will also have structural identity to SEQ ID NO: 2 and/orSEQ ID NO:3. In some embodiments, the variant having increasedthermostability has a substitution in at least one of the positions: 10,42, 68, 73, 97, 153, 229, 231, 236, 264, 291, 301, 344, 361, 364, 375,and/or 417 of SEQ ID NO: 2 and/or SEQ ID NO:3. In some embodiments, thevariant having increased thermostability has a substitution in at leastone of the positions: 42, 68, 73, 153, 236, 344, 361, 364, and/or 365 ofSEQ ID NO: 2 and/or SEQ ID NO:3.

SBD Variants with Increased Specific Activity:

In some embodiments, a variant glucoamylase encompassed by the inventionwill have an altered specific activity as compared to a parent or wildtype glucoamylase. In some embodiments, the altered specific activity isincreased specific activity. Increased specific activity can be definedas an increased performance index (PI) of greater than or equal to about1.0, including greater than or equal to about 1.1, 1.2, 1.3, 1.4, 1.5,1.6, 1.7, 1.8, 1.9, 2, 2.3, 2.5, 3.0, 3.3, 3.5, 4.0, 4.3, 4.5 and evengreat than or equal to 5.0. In some embodiments, the variant has an atleast 1 fold higher specific activity than the parent glucoamylase,including at least 1.1 fold, 1.2 fold, 1.3 fold, 1.4 fold, 1.5 fold, 1.6fold, 1.7 fold, 1.8 fold, 1.9 fold, 2 fold, 2.2 fold, 2.5 fold, 2.7fold, 2.9 fold, 3 fold, 4 fold, and 5 fold.

In some embodiments, glucoamylase variants encompassed by the inventionhaving increased specific activity include those having one or moresubstitutions in the following positions in the amino acid sequence setforth in SEQ ID NO:2: 493, 494, 495, 502, 503, 508, 511, 518, 519, 520,531, 535, 536, and 539, and/or an equivalent position in a parentglucoamylase. In some embodiments, the variants include one or moresubstitutions in the SBD. In some embodiments, the variants of theinvention having improved specific activity include a substitutioncorresponding to position 495, 519, 520, 535, and 539 of SEQ ID NO: 2.In some embodiments, variants of the invention having improved specificactivity include a substitution chosen from: T493C, T493M, T493N, T493Q,T493Y, P494H, P494I, P494M, P494N, P494Q, P494W, T495M, T495P, T495R,H502A, H502M, H502S, H502V, E503C, E503D, E503H, E503S, E503W, Q508N,Q508P, Q508Y, Q511C, Q511G, Q511H, Q511, Q511K, Q511T, Q511V, N518P,N515T, A519I, A520C, A520E, A520L, A520P, A520Q, A520R, A520W, V531A,V5311L, V531N, V531R, V531S, V531T, A535E, A535F, A535G, A535K, A535L,A535N, A535P, A535R, A535S, A535T, A535V, A535W, A535Y, V536C, V536E,V536I V536L, V536M, V536Q, V536S, A539E, A539M, A539R, A539S, and A539Wand/or an equivalent position in a parent glucoamylase. In someembodiments, the variants of the invention having an improved specificactivity include a substitution corresponding to position T495M, A519I,A520C/L/P, A535R and A539R. In some embodiments, the parent glucoamylasewill comprise a sequence having at least 80%, at least 85%, at least90%, at least 95% or 97% sequence identity to the sequence of SEQ IDNO:2.

In further embodiments, glucoamylase variants encompassed by theinvention having increased specific activity include the SBD variantsdelineated in the paragraph above and additionally include one or moredeletions, substitutions or insertions and particularly substitutions inthe following positions in the amino acid sequence set forth in SEQ IDNO:2 and/or SEQ ID NO:3: T10, L14, N15, P23, F59, K60, N61, T67, E68,A72, G73, S97, L98, A99, S102, E110, L113, I133, K140, N144, N145, Y147,S152, N153, N164, N182, A204, T205, S214, V216, Q219, W228, V229, S230,S231, D236, I239, T241, N242, N263, L264, G265, A268, G269, D276, V284,S291, P300, A301, A311, V338, T342, S344, T346, A349, V359, G361, A364,T375, N379, S382, S390, E391, A393, K394, S410, S415, L417, H418, T430,A431, R433, A442, S444, T448 and/or S451 and/or an equivalent positionin a parent glucoamylase. In some embodiments, variants of the inventionhaving improved specific activity include a substitution in thefollowing positions in the amino acid sequence set forth in SEQ ID NO: 2or SEQ ID NO:3: 61, 67, 72, 97, 102, 133, 205, 219, 228, 230, 231, 239,263, 268, 291, 342, 394, 430, 431 and 451 and/or an equivalent positionin a parent glucoamylase. In some embodiments, the parent glucoamylasewill comprise a sequence having at least 50%, at least 60%, at least70%, at least 80%, at least 90% or 95% sequence identity to the sequenceof SEQ ID NO:2 or SEQ ID NO:3. In some embodiments, the parentglucoamylase will also have structural identity to SEQ ID NO: 2 and/orSEQ ID NO:3. In some embodiments, the variant having increased specificactivity has a substitution in at least one of the positions: 72, 133,219, 228, 230, 231, 239, 263, 268, and 451 of SEQ ID NO: 2 and/or SEQ IDNO:3.

SBD Variants Having Both Increased Thermostability and Increase SpecificActivity

In some aspects, the invention relates to a variant glucoamylase havingboth altered thermal stability and altered specific activity as comparedto a parent or wild type. In some embodiments, the altered specificactivity is an increased specific activity and the alteredthermostability is an increased thermostability as compared to theparent glucoamylase.

In some embodiments, glucoamylase variants encompassed by the inventionhaving increased thermostability and increased specific activity includethose having one or more substitutions, insertions or deletions, andparticularly substitutions in the following positions in the amino acidsequence set forth in SEQ ID NO:2: 493, 495, 503, 508, 511, 518, 519,520, 527, 531, 535, 536, 537, 539, 563, and 577 and/or an equivalentposition in a parent glucoamylase.

In some embodiments, glucoamylase variants encompassed by the inventionhaving increased thermostability and increased specific activity includethose having one or more substitutions, insertions or deletions, andparticularly substitutions in the following positions in the amino acidsequence set forth in SEQ ID NO:2: 495, 503, 511, 520, 531, 535, 536,and 539 and/or an equivalent position in a parent glucoamylase. Infurther embodiments, glucoamylase variant encompassed by the inventionhaving increased thermostability and increased specific activity includethe following substitutions T495R, E503C/S, Q511H, A520C/L/P, V531L,A535K/N/P/R, V536I, and A539E/M/R/S.

In some embodiments, the parent glucoamylase will be a Trichodermaglucoamylase homologue and in further embodiments, the parentglucoamylase will have at least 90%, at least 95% and at least 98%sequence identity to SEQ ID NO:2. In some embodiments, the varianthaving increased thermostability and increased specific activity has asubstitution in at least one of the positions: 503, 511, 519, 531, 535,539, 563, and 577. In some embodiments, the substitutions are chosenfrom: T4931, T495K, T495R, T495S, E503A, E503C, E503S, E503T, E503V,Q508H, Q508R, Q508S, Q508T, Q511A, Q511D, Q511H, Q511N, Q511S, N518S,A519E, A519K, A519R, A519T, A519V, A519Y, A520C, A520L, A520P, T527A,T527V, V531L, A535D, A535K, A535N, A535P, A535R, V536I, V536R, N537W,A539E, A539H, A539M, A539R, A539S, N563A, N563C, N563E, N5631, N563K,N563L, N563Q, N563T, N563V, N577A, N577K, N577P, N577R, and N577V of SEQID NO:2.

In further embodiments, glucoamylase variants encompassed by theinvention having increased specific activity and increasedthermostability include the SBD variants delineated in the paragraphabove and additionally include one or more deletions, substitutions orinsertions and particularly substitutions in the following positions inthe amino acid sequence set forth in SEQ ID NO:2 and/or SEQ ID NO:3:T10, N15, F59, N61, E68, A72, G73, S97, A99, S102, I133, K140, N153,N182, A204, T205, S214, W228, V229, S230, S231, D236, T241, N242, L264,G265, A268, D276, V284, S291, P300, A301, A303, A311, V338, S344, T346,V359, G361, A364, T375, N379, S382, E391, A393, K394, S410, L417, T430,A431, R433, S444, T448 and/or S451 and/or an equivalent position in aparent glucoamylase. In some embodiments, the parent glucoamylase willbe a Trichoderma glucoamylase homologue and in further embodiments, theparent glucoamylase will have at least 50%, at least 60%, at least 70%,at least 80%, at least 90%, at least 95% and at least 98% sequenceidentity to SEQ ID NO:2 or SEQ ID NO:3. In some embodiments, the parentglucoamylase will also have structural identity to SEQ ID NO: 2 and/orSEQ ID NO:3. In some embodiments, the variant having increasedthermostability and specific activity has a substitution in at least oneof the positions: 228, 230, 231, 268, 291, 417, 433, and 451 of SEQ IDNO: 2 and/or SEQ ID NO:3.

Polynucleotides:

The present invention also relates to isolated polynucleotides encodinga SBD variant glucoamylase of the invention. The polynucleotides can beprepared by established techniques known in the art. The polynucleotidescan be prepared synthetically, such as by an automatic DNA synthesizer.The DNA sequence can be of mixed genomic (or cDNA) and synthetic originprepared by ligating fragments together. The polynucleotides can also beprepared by polymerase chain reaction (PCR) using specific primers. Ingeneral, reference is made to Minshull J., et al., (2004), Methods32(4):416-427). Also a number of companies now synthesize DNA such asGeneart AG, Regensburg, Germany.

In some embodiments an isolated polynucleotide comprises a nucleotidesequence (i) having at least 70% identity to SEQ ID NO:4, or (ii) beingcapable of hybridizing to a probe derived from the nucleotide sequenceset forth in SEQ ID NO:4, under conditions of intermediate to highstringency, or (iii) being complementary to a nucleotide sequence havingat least 90% sequence identity to the sequence set forth in SEQ ID NO:4.Probes useful according to the invention may include at least 50, 100,150, 200, 250, 300 or more contiguous nucleotides of SEQ ID NO:4.

The present invention further provides isolated polynucleotides thatencode variant glucoamylases having one or more amino acid substitutionscorresponding to positions 3, 4, 5, 12, 13, 18, 21, 28, 29, 30, 37, 41,45, 46, 47, 49, 73, and 87 of SEQ ID NO: 11 or an equivalent position ofa SBD of a parent glucoamylase. In some embodiments, the parentglucoamylase will have an amino acid sequence comprising at least 50%sequence identity, at least 60% sequence identity, at least 70% sequenceidentity, at least 80% sequence identity, at least 85% sequenceidentity, at least 90% sequence identity, at least 95% sequence identityat least 97% sequence identity, at least 98% amino acid sequence and atleast 99% amino acid sequence identity to SEQ ID NO: 11.

The present invention also provides fragments (i.e., portions) of theDNA encoding the variant glucoamylases provided herein. These fragmentsfind use in obtaining partial length DNA fragments capable of being usedto isolate or identify polynucleotides encoding mature glucoamylaseenzymes described herein from filamentous fungal cells (e.g.,Trichoderma, Aspergillus, Fusarium, Penicillium, and Humicola), or asegment thereof having glucoamylase activity. In some embodiments,fragments of the DNA may comprise at least 50, 100, 150, 200, 250 300 ormore contiguous nucleotides. In some embodiments, portions of the DNAprovided in SEQ ID NO:11 find use in obtaining parent glucoamylase andparticularly Trichoderma glucoamylase homologues from other species,such as filamentous fungi which encode a glucoamylase.

DNA Constructs and Vectors:

According to some embodiments of the invention, a DNA constructcomprising a polynucleotide as described above encoding a variantglucoamylase encompassed by the invention and operably linked to apromoter sequence is assembled to transfer into a host cell.

The DNA construct may be introduced into a host cell using a vector. Thevector may be any vector which when introduced into a host cell can beintegrated into the host cell genome and is replicated. In someembodiments, the vector is stably transformed and/or integrated into thehost cell. Vectors include cloning vectors, expression vectors, shuttlevectors, plasmids, phage particles, cassettes and the like. In someembodiments, the vector is an expression vector that comprisesregulatory sequences operably linked to the glucoamylase codingsequence.

Examples of suitable expression and/or integration vectors are providedin Sambrook et al., (1989) supra, and Ausubel (1987) supra, and van denHondel et al. (1991) in Bennett and Lasure (Eds.) MORE GENEMANIPULATIONS IN FUNGI, Academic Press pp. 396-428 and U.S. Pat. No.5,874,276. Reference is also made to the Fungal Genetics Stock CenterCatalogue of Strains (FGSC, <www.fgsc.net>) for a list of vectors.Particularly useful vectors include vectors obtained from for exampleInvitrogen and Promega.

Suitable plasmids for use in bacterial cells include pBR322 and pUC19permitting replication in E. coli and pE194 for example permittingreplication in Bacillus. Other specific vectors suitable for use in E.coli host cells include vectors such as pFB6, pBR322, pUC18, pUC100,pDONR™201, pDONR™221, pENTR™, pGEM®3Z and pGEM®4Z.

Specific vectors suitable for use in fungal cells include pRAX, ageneral purpose expression vector useful in Aspergillus, pRAX with aglaA promoter, and in Hypocrea/Trichoderma includes pTrex3g with a cbh1promoter.

In some embodiments, the promoter shows transcriptional activity in abacterial or a fungal host cell and may be derived from genes encodingproteins either homologous or heterologous to the host cell. Thepromoter may be a mutant, a truncated and/or a hybrid promoter. Theabove-mentioned promoters are known in the art. Examples of suitablepromoters useful in fungal cells and particularly filamentous fungalcells such as Trichoderma or Aspergillus cells include such exemplarypromoters as the T. reesei promoters cbh1, cbh2, egl1, egl2, eg5, xln1and xln2. Other examples of useful promoters include promoters from A.awamori and A. niger glucoamylase genes (glaA) (See, Nunberg et al.,(1984) Mol. Cell. Biol. 4:2306-2315 and Boel et al., (1984) EMBO J.3:1581-1585), A. oryzae TAKA amylase promoter, the TPI (triose phosphateisomerase) promoter from S. cerevisiae, the promoter from Aspergillusnidulans acetamidase genes and Rhizomucor miehei lipase genes. Examplesof suitable promoters useful in bacterial cells include those obtainedfrom the E. coli lac operon; Bacillus licheniformis alpha amylase gene(amyL), B. stearothermophilus amylase gene (amyS); Bacillus subtilisxylA and xylB genes, the beta-lactamase gene, and the tac promoter. Insome embodiments, the promoter is one that is native to the host cell.For example, when T. reesei is the host, the promoter is a native T.reesei promoter. In other embodiments, the promoter is one that isheterologous to the fungal host cell. In some embodiments the promoterwill be the parent glucoamylase promoter (e.g., the TrGA promoter).

In some embodiments, the DNA construct includes nucleic acids coding fora signal sequence, that is, an amino acid sequence linked to the aminoterminus of the polypeptide which directs the encoded polypeptide intothe cell's secretory pathway. The 5′ end of the coding sequence of thenucleic acid sequence may naturally include a signal peptide codingregion which is naturally linked in translation reading frame with thesegment of the glucoamylase coding sequence which encodes the secretedglucoamylase or the 5′ end of the coding sequence of the nucleic acidsequence may include a signal peptide which is foreign to the codingsequence. In some embodiments, the DNA construct includes a signalsequence that is naturally associated with a parent glucoamylase genefrom which a variant glucoamylase has been obtained. In some embodimentsthe signal sequence will be the sequence depicted in SEQ ID NO:1 or asequence having at least 90%, at least 94% and at least 98% sequenceidentity thereto. Effective signal sequences may include the signalsequences obtained from other filamentous fungal enzymes, such as fromTrichoderma (T. reesei glucoamylase), Humicola (H insolens cellulase orH. grisea glucoamylase), Aspergillus (A. niger glucoamylase and A.oryzae TAKA amylase), and Rhizopus.

In additional embodiments, a DNA construct or vector comprising a signalsequence and a promoter sequence to be introduced into a host cell arederived from the same source. In some embodiments, the nativeglucoamylase signal sequence of a Trichoderma glucoamylase homologue,such as a signal sequence from a Hypocrea strain may be used.

In some embodiments, the expression vector also includes a terminationsequence. Any termination sequence functional in the host cell may beused in the present invention. In some embodiments, the terminationsequence and the promoter sequence are derived from the same source. Inanother embodiment, the termination sequence is homologous to the hostcell. Useful termination sequences include termination sequencesobtained from the genes of Trichoderma reesei cbh1; A. niger or A.awamori glucoamylase (Nunberg et al. (1984) supra, and Boel et al.,(1984) supra), Aspergillus nidulans anthranilate synthase, Aspergillusoryzae TAKA amylase, or A. nidulans trpC (Punt et al., (1987) Gene56:117-124).

In some embodiments, an expression vector includes a selectable marker.Examples of selectable markers include ones which confer antimicrobialresistance (e.g., hygromycin and phleomycin). Nutritional selectivemarkers also find use in the present invention including those markersknown in the art as amdS (acetamidase), argB (ornithinecarbamoyltransferase) and pyrG (orotidine-5′phosphate decarboxylase).Markers useful in vector systems for transformation of Trichoderma areknown in the art (See, e.g., Finkelstein, chapter 6 in BIOTECHNOLOGY OFFILAMENTOUS FUNGI, Finkelstein et al. Eds, Butterworth-Heinemann,Boston, Mass. (1992); Kinghorn et al. (1992) APPLIED MOLECULAR GENETICSOF FILAMENTOUS FUNGI, Blackie Academic and Professional, Chapman andHall, London; Berges and Barreau (1991) Curr. Genet. 19:359-365; and vanHartingsveldt et al., (1987) Mol. Gen. Genet. 206:71-75). In someembodiments, the selective marker is the amdS gene, which encodes theenzyme acetamidase, allowing transformed cells to grow on acetamide as anitrogen source. The use of A. nidulans amdS gene as a selective markeris described in Kelley et al., (1985) EMBO J. 4:475-479 and Penttilä etal., (1987) Gene 61:155-164.

Methods used to ligate the DNA construct comprising a nucleic acidsequence encoding a variant glucoamylase, a promoter, a termination andother sequences and to insert them into a suitable vector are well knownin the art. Linking is generally accomplished by ligation at convenientrestriction sites. If such sites do not exist, synthetic oligonucleotidelinkers are used in accordance with conventional practice. (See,Sambrook (1989) supra, and Bennett and Lasure, MORE GENE MANIPULATIONSIN FUNGI, Academic Press, San Diego (1991) pp 70-76.). Additionally,vectors can be constructed using known recombination techniques (e.g.,Invitrogen Life Technologies, Gateway Technology).

Host Cells:

Some embodiments of the invention include host cells comprising apolynucleotide encoding a variant glucoamylase of the invention. In someembodiments, the host cells are chosen from bacterial, fungal, plant andyeast cells. The term host cell includes both the cells, progeny of thecells and protoplasts created from the cells which are used to produce avariant glucoamylase according to the invention.

In some embodiments, the host cells are fungal cells. In someembodiments, the host cells are filamentous fungal host cells. The term“filamentous fungi” refers to all filamentous forms of the subdivisionEumycotina (See, Alexopoulos, C. J. (1962), INTRODUCTORY MYCOLOGY,Wiley, New York). These fungi are characterized by a vegetative myceliumwith a cell wall composed of chitin, cellulose, and other complexpolysaccharides. The filamentous fungi of the present invention aremorphologically, physiologically, and genetically distinct from yeasts.Vegetative growth by filamentous fungi is by hyphal elongation andcarbon catabolism is obligatory aerobic. In the present invention, thefilamentous fungal parent cell may be a cell of a species of, but notlimited to, Trichoderma, (e.g., Trichoderma reesei, the asexual morph ofHypocrea jecorina, previously classified as T. longibrachiatum,Trichoderma viride, Trichoderma koningii, Trichoderma harzianum)(Sheir-Neirs et al., (1984) Appl. Microbiol. Biotechnol 20:46-53; ATCCNo. 56765 and ATCC No. 26921); Penicillium sp., Humicola sp. (e.g., H.insolens, H. lanuginosa and H. grisea); Chrysosporium sp. (e.g., C.lucknowense), Gliocladium sp., Aspergillus sp. (e.g., A. oryzae, A.niger, A sojae, A. japonicus, A. nidulans, and A. awamori) (Ward et al.,(1993) Appl. Microbiol. Biotechnol. 39:738-743 and Goedegebuur et al.,(2002) Genet. 41:89-98), Fusarium sp. (e.g. F. roseum, F. graminum F.cerealis, F. oxysporum and F. venenatum), Neurospora sp., (N. crassa),Hypocrea sp., Mucor sp., (M. miehei), Rhizopus sp. and Emericella sp.(See also, Innis et al., (1985) Sci. 228:21-26). The term “Trichoderma”or “Trichoderma sp.” or “Trichoderma spp.” refer to any fungal genuspreviously or currently classified as Trichoderma.

In some embodiments, the host cells will be gram-positive bacterialcells. Non-limiting examples include strains of Streptomyces, (e.g., S.lividans, S. coelicolor and S. griseus) and Bacillus. As used herein,“the genus Bacillus” includes all species within the genus “Bacillus,”as known to those of skill in the art, including but not limited to B.subtilis, B. licheniformis, B. lentus, B. brevis, B. stearothermophilus,B. alkalophilus, B. amyloliquefaciens, B. clausii, B. halodurans, B.megaterium, B. coagulans, B. circulans, B. lautus, and B. thuringiensis.It is recognized that the genus Bacillus continues to undergotaxonomical reorganization. Thus, it is intended that the genus includespecies that have been reclassified, including but not limited to suchorganisms as B. stearothermophilus, which is now named “Geobacillusstearothermophilus.”

In some embodiments the host cell is a gram-negative bacterial strain,such as E. coli or Pseudomonas sp. In other embodiments, the host cellsmay be yeast cells such as Saccharomyces sp., Schizosaccharomyces sp.,Pichia sp., or Candida sp.

In other embodiments, the host cell will be a genetically engineeredhost cell wherein native genes have been inactivated, for example bydeletion in bacterial or fungal cells. Where it is desired to obtain afungal host cell having one or more inactivated genes known methods maybe used (e.g. methods disclosed in U.S. Pat. No. 5,246,853, U.S. Pat.No. 5,475,101 and WO 92/06209). Gene inactivation may be accomplished bycomplete or partial deletion, by insertional inactivation or by anyother means which renders a gene nonfunctional for its intended purpose(such that the gene is prevented from expression of a functionalprotein). In some embodiments, when the host cell is a Trichoderma celland particularly a T. reesei host cell, the cbh1, cbh2, egl1 and egl2genes will be inactivated and can be deleted. In some embodiments, theTrichoderma reesei host cells have quad-deleted gene coding for proteinssuch as those set forth and described in U.S. Pat. No. 5,847,276 and WO05/001036. In other embodiments, the host cell is a protease deficientor protease minus strain.

Transformation of Host Cells:

Introduction of a DNA construct or vector into a host cell includestechniques such as transformation; electroporation; nuclearmicroinjection; transduction; transfection, (e.g., lipofection-mediatedand DEAE-Dextrin mediated transfection); incubation with calciumphosphate DNA precipitate; high velocity bombardment with DNA-coatedmicroprojectiles; and protoplast fusion. General transformationtechniques are known in the art (See, e.g., Ausubel et al., (1987),supra, chapter 9; and Sambrook (1989) supra, and Campbell et al., (1989)Curr. Genet. 16:53-56).

Transformation methods for Bacillus are disclosed in numerous referencesincluding Anagnostopoulos C and J. Spizizen (1961) J. Bacteriol.81:741-746 and WO 02/14490.

Transformation methods for Aspergillus are described in Yelton et al(1984) Proc. Natl. Acad. Sci. USA 81:1470-1474; Berka et al., (1991) inApplications of Enzyme Biotechnology, Eds. Kelly and Baldwin, PlenumPress (NY); Cao et al., (2000) Sci. 9:991-1001; Campbell et al., (1989)Curr. Genet. 16:53-56 and EP 238 023. The expression of heterologousprotein in Trichoderma is described in U.S. Pat. No. 6,022,725; U.S.Pat. No. 6,268,328; Harkki et al. (1991); Enzyme Microb. Technol.13:227-233; Harkki et al., (1989) Bio Technol. 7:596-603; EP 244,234; EP215,594; and Nevalainen et al., “The Molecular Biology of Trichodermaand its Application to the Expression of Both Homologous andHeterologous Genes”, in MOLECULAR INDUSTRIAL MYCOLOGY, Eds. Leong andBerka, Marcel Dekker Inc., NY (1992) pp. 129-148). Reference is alsomade to WO96/00787 and Bajar et al., (1991) Proc. Natl. Acad. Sci. USA88:8202-28212 for transformation of Fusarium strains.

In one specific embodiment, the preparation of Trichoderma sp. fortransformation involves the preparation of protoplasts from fungalmycelia (See, Campbell et al., (1989) Curr. Genet. 16:53-56; Pentilla etal., (1987) Gene 61:155-164). Agrobacterium tumefaciens-mediatedtransformation of filamentous fungi is known (See, de Groot et al.,(1998) Nat. Biotechnol. 16:839-842). Reference is also made to U.S. Pat.No. 6,022,725 and U.S. Pat. No. 6,268,328 for transformation proceduresused with filamentous fungal hosts.

In some embodiments, genetically stable transformants are constructedwith vector systems whereby the nucleic acid encoding the variantglucoamylase is stably integrated into a host strain chromosome.Transformants are then purified by known techniques.

In some further embodiments, the host cells are plant cells, such ascells from a monocot plant (e.g. corn, wheat and sorghum) or cells froma dicot plant (e.g. soybean). Methods for making DNA constructs usefulin transformation of plants and methods for plant transformation areknown. Some of these methods include Agrobacterium tumefaciens mediatedgene transfer; microprojectile bombardment, PEG mediated transformationof protoplasts, electroporation and the like. Reference is made to U.S.Pat. No. 6,803,499, U.S. Pat. No. 6,777,589; Fromm et al (1990)Biotechnol. 8:833-839; Potrykus et al (1985) Mol. Gen. Genet.199:169-177.

Production of Proteins:

In some embodiments, the invention is directed to methods of producingthe glucoamylase variants in a host cell. In some embodiments, themethod comprises transforming a host cell with a vector comprising apolynucleotide encoding a variant glucoamylase according to theinvention, optionally culturing the host cell under conditions suitablefor expression and production of the glucoamylase variant and optionallyrecovering the variant. Suitable culture conditions include but are notlimited to shake flask cultivation, small scale or large scalefermentations (including continuous, batch and fed batch fermentations)in laboratory or industrial fermentors, with suitable medium containingphysiological salts and nutrients (See, e.g., Pourquie, J. et al.,BIOCHEMISTRY AND GENETICS OF CELLULOSE DEGRADATION, eds. Aubert, J. P.et al., Academic Press, pp. 71-86, 1988 and Ilmen, M. et al., (1997)Appl. Environ. Microbiol. 63:1298-1306). Common commercially preparedmedia (e.g., Yeast Malt Extract (YM) broth, Luria Bertani (LB) broth andSabouraud Dextrose (SD) broth) find use in the present invention.Culture conditions for bacterial and filamentous fungal cells are knownin the art and may be found in the scientific literature and/or from thesource of the fungi such as the American Type Culture Collection andFungal Genetics Stock Center. In cases where a glucoamylase codingsequence is under the control of an inducible promoter, the inducingagent (e.g., a sugar, metal salt or antimicrobial), is added to themedium at a concentration effective to induce glucoamylase expression.

In some embodiments, assays are carried out to evaluate the expressionof a glucoamylase variant by a cell line that has been transformed witha polynucleotide encoding a variant encompassed by the invention. Theassays can be carried out at the protein level, the RNA level and/or byuse of functional bioassays particular to glucoamylase activity and/orproduction. Some of these assays include Northern blotting, dot blotting(DNA or RNA analysis), RT-PCR (reverse transcriptase polymerase chainreaction), in situ hybridization using an appropriately labeled probe(based on the nucleic acid coding sequence) and conventional Southernblotting and autoradiography.

In addition, the production and/or expression of a variant glucoamylaseencompassed by the invention may be measured in a sample directly, forexample, by assays directly measuring reducing sugars such as glucose inthe culture medium and by assays for measuring glucoamylase activity,expression and/or production. In particular, glucoamylase activity maybe assayed by the 3,5-dinitrosalicylic acid (DNS) method (See, Goto etal., (1994) Biosci. Biotechnol. Biochem. 58:49-54). In additionalembodiments, protein expression, is evaluated by immunological methods,such as immunohistochemical staining of cells, tissue sections orimmunoassay of tissue culture medium, (e.g., by Western blot or ELISA).Such immunoassays can be used to qualitatively and quantitativelyevaluate expression of a glucoamylase. The details of such methods areknown to those of skill in the art and many reagents for practicing suchmethods are commercially available.

The SBD variant glucoamylases of the present invention may be recoveredor purified from culture media by a variety of procedures known in theart including centrifugation, filtration, extraction, precipitation andthe like.

Compositions:

The glucoamylase variants may be used in enzyme compositions includingbut not limited to starch hydrolyzing and saccharifying compositions,cleaning and detergent compositions (e.g., laundry detergents, dishwashing detergents, and hard surface cleaning compositions), alcoholfermentation compositions, animal feed compositions and beveragecompositions. Further the variants may be used in baking applications,such as bread and cake production, brewing, healthcare, textile,environmental waste conversion processes, biopulp processing, andbiomass conversion applications.

In some embodiments, an enzyme composition including a SBD variantencompassed by the invention will be obtained in culture media orrecovered and purified from the culture medium. In some embodiments, theSBD variant will be used in combination with any one or combination ofthe following enzymes—alpha amylases, proteases, pullulanases,isoamylases, cellulases, hemicellulases, xylanases, cyclodextringlycotransferases, lipases, phytases, laccases, oxidases, esterases,cutinases, xylanases, granular starch hydrolyzing enzyme and otherglucoamylases.

In some compositions the SBD variant of the invention will be combinedwith an alpha amylase, such as fungal alpha amylases (e.g. Aspergillussp.) or bacterial alpha amylases (e.g. Bacillus sp. such as B.stearothermophilus, B. amyloliquefaciens and B. licheniformis) andvariants and hybrids thereof. In some embodiments the alpha amylase isan acid stable alpha amylase. In some embodiments, the alpha amylase isa granular starch hydrolyzing enzyme (GSHE). In some embodiments, thealpha amylase is Aspergillus kawachi alpha amylase (AKAA), see U.S. Pat.No. 7,037,704. Commercially available alpha amylases contemplated foruse in the compositions of the invention are known and include GZYMEG997, SPEZYME FRED, SPEZYME XTRA, STARGEN (Danisco US, Inc, GenencorDivision), TERMAMYL 120-L and SUPRA (Novozymes, Biotech.) and VIRIDIUM(Diversa).

In some embodiments, the proteases are acid fungal proteases. In afurther embodiment, the acid fungal proteases are from Trichoderma(e.g., NSP-24, see also US 2006/015342, published Jul. 13, 2006, SEQ IDNO: 10, incorporated by reference).

In other embodiments, the glucoamylase variants of the invention may becombined with other glucoamylases. In some embodiments, theglucoamylases of the invention will be combined with one or moreglucoamylases derived from strains of Aspergillus or variants thereof,such as A. oryzae, A. niger, A. kawachi, and A. awamori; glucoamylasesderived from strains of Humicola or variants thereof, particularly H.grisea, such as the glucoamylase having at least 90%, 93%, 95%, 96%,97%, 98% and 99% sequence identity to SEQ ID NO: 3 disclosed in WO05/052148; glucoamylases derived from strains of Talaromyces or variantsthereof, particularly T. emersonii; glucoamylases derived from strainsof Athelia and particularly A. rolfsii; glucoamylases derived fromstrains of Penicillium, particularly P. chrysogenum.

Uses:

In particular, the SBD variants may be used for starch conversionprocesses, and particularly in the production of dextrose for fructosesyrups, specialty sugars and in alcohol (e.g., ethanol and butanol) andother end-product (e.g. organic acid, ascorbic acid, and amino acids)production from fermentation of starch containing substrates (G. M. Avan Beynum et al., Eds. (1985) STARCH CONVERSION TECHNOLOGY, MarcelDekker Inc. NY). Dextrins produced using glucoamylase variantcompositions of the invention may result in glucose yields of at least80%, at least 85%, at least 90% and at least 95%. Production of alcoholfrom the fermentation of starch substrates using glucoamylasesencompassed by the invention may include the production of fuel alcoholor potable alcohol. In some embodiments, the production of alcohol willbe greater when the glucoamylase variant is used under the sameconditions as the parent glucoamylase. In some embodiments, theproduction of alcohol will be between about 0.5% and 2.5% greater,including but not limited to 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%,1.3%, 1.4%, 1.5%, 1.6%. 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, and2.4% more alcohol than the parent glucoamylase under essentially thesame conditions.

In some embodiments, the SBD variant glucoamylases of the invention willfind use in the hydrolysis of starch from various plant-basedsubstrates, which are used for alcohol production. In some embodiments,the plant-based substrates will include corn, wheat, barley, rye, milo,rice, sugar cane, potatoes and combinations thereof. In someembodiments, the plant-based substrate will be fractionated plantmaterial, for example a cereal grain such as corn, which is fractionatedinto components such as fiber, germ, protein and starch (endosperm)(U.S. Pat. No. 6,254,914 and U.S. Pat. No. 6,899,910). Methods ofalcohol fermentations are described in THE ALCOHOL TEXTBOOK, A REFERENCEFOR THE BEVERAGE, FUEL AND INDUSTRIAL ALCOHOL INDUSTRIES, 3^(rd) Ed.,Eds K. A. Jacques et al., 1999, Nottingham University Press, UK. Incertain embodiments, the alcohol will be ethanol. In particular, alcoholfermentation production processes are characterized as wet milling ordry milling processes. In some embodiments, the variant glucoamylasewill be used in a wet milling fermentation process and in otherembodiments the variant glucoamylase will find use in a dry millingprocess.

Dry grain milling involves a number of basic steps, which generallyinclude: grinding, cooking, liquefaction, saccharification, fermentationand separation of liquid and solids to produce alcohol and otherco-products. Plant material and particularly whole cereal grains, suchas corn, wheat or rye are ground. In some cases the grain may be firstfractionated into component parts. The ground plant material may bemilled to obtain a coarse or fine particle. The ground plant material ismixed with liquid (e.g. water and/or thin stillage) in a slurry tank.The slurry is subjected to high temperatures (e.g. 90° C. to 105° C. orhigher) in a jet cooker along with liquefying enzymes (e.g. alphaamylases) to solubilize and hydrolyze the starch in the grain todextrins. The mixture is cooled down and further treated withsaccharifying enzymes, such as glucoamylases encompassed by the instantinvention, to produce glucose. The mash containing glucose may then befermented for approximately 24 to 120 hours in the presence offermentation microorganisms, such as ethanol producing microorganism andparticularly yeast (Saccharomyces spp). The solids in the mash areseparated from the liquid phase and alcohol such as ethanol and usefulco-products such as distillers' grains are obtained.

In some embodiments, the saccharification step and fermentation step arecombined and the process is referred to as simultaneous saccharificationand fermentation or simultaneous saccharification, yeast propagation andfermentation.

In other embodiments, the SBD variant glucoamylase is used in a processfor starch hydrolysis wherein the temperature of the process is between30° C. and 75° C., in some embodiments, between 40° C. and 65° C. Insome embodiments, the variant glucoamylase is used in a process forstarch hydrolysis at a pH of between pH 3.0 and pH 6.5. The fermentationprocesses in some embodiments include milling of a cereal grain orfractionated grain and combining the ground cereal grain with liquid toform a slurry which is then mixed in a single vessel with a variantglucoamylase according to the invention and optionally other enzymessuch as, but not limited to, alpha amylases, other glucoamylases,phytases, proteases, pullulanases, isoamylases or other enzymes havinggranular starch hydrolyzing activity and yeast to produce ethanol andother co-products (See e.g., U.S. Pat. No. 4,514,496, WO 04/081193 andWO 04/080923).

In some embodiments, the invention pertains to a method of saccharifyinga liquid starch solution, which comprises an enzymatic saccharificationstep using a variant glucoamylase of the invention.

The present invention also provides an animal feed composition orformulation comprising at least one SBD variant glucoamylase encompassedby the invention. Methods of using an SBD variant glucoamylase enzyme inthe production of feeds comprising starch are provided in WO 03/049550,filed Dec. 13, 2002 (herein incorporated by reference in its entirety).Briefly, the SBD glucoamylase variant is admixed with a feed comprisingstarch. The SBD glucoamylase variant is capable of degrading resistantstarch for use by the animal.

Experimental

In the disclosure and experimental section which follows, the followingabbreviations apply: GA (glucoamylase); GAU (glucoamylase unit); wt %(weight percent); ° C. (degrees Centigrade); rpm (revolutions perminute); H₂O (water); dH₂O (deionized water); dIH₂O (deionized water,Milli-Q filtration); aa or AA (amino acid); bp (base pair); kb (kilobasepair); kD (kilodaltons); g or gm (grams); μg (micrograms); mg(milligrams); IL (microliters); ml and mL (milliliters); mm(millimeters); m (micrometer); M (molar); mM (millimolar); μM(micromolar); U (units); V (volts); MW (molecular weight); sec(s) ors(s) (second/seconds); min(s) or m(s) (minute/minutes); hr(s) or h(s)(hour/hours); DO (dissolved oxygen); ABS (Absorbance); EtOH (ethanol);PSS (physiological salt solution); m/v (mass/volume); and MTP(microtiter plate); N (Normal); DP1 (monosaccharides); DP2(disaccharides); DP>3 (oligosaccharides, sugars having a degree ofpolymerization greater than 3); ppm (parts per million).

The following assays and methods were used in the examples providedbelow. However, it should be noted that different methods may be used toprovide variants of a parent molecule and the invention is not limitedto the methods used in the examples. It is intended that any suitablemeans for making variants and selection of variants may be used.

pNPG Glucoamylase Activity Assay for 96-Well Microtiter Plates:

The reagent solutions were: NaAc buffer (200 mM sodium acetate buffer pH4.5); Substrate (50 mM p-nitrophenyl-α-D-glucopyranoside (Sigma N-1377)in NaAc buffer (0.3 g/20 ml)) and stop solution (800 mM glycine-NaOHbuffer pH 10). 30 μl filtered supernatant was placed in a fresh 96-wellflat bottom MTP. To each well 50 μl NaAc buffer and 120 μl substrate wasadded and incubated for 30 minutes at 50° C. (Thermolab systems iEMSIncubator/shaker HT). The reaction was terminated by adding 100 μl stopsolution. The absorbance was measured at 405 nm in a MTP-reader(Molecular Devices Spectramax 384 plus) and the activity was calculatedusing a molar extinction coefficient of 0.011 μM/cm.

Thermostability Assay:

Crude supernatant (8 μl) was added to 280 μl 50 mM NaAc buffer pH 4.5.The diluted sample was equally divided over 2 MTPs. One MTP (initialplate) was incubated for 1 hr at 4° C. and the other MTP (residualplate) was incubated at 64° C. (Thermolab systems iEMS Incubator/ShakerHT) for 1 hr. The residual plate was chilled for 10 min on ice. Activitywas measured of both plates using the ethanol screening assay describedbelow. 60 μl of the initial plate or residual plate was added to 120 μl4% soluble corn starch and incubated for 2 hrs at 32° C. 900 rpm(Thermolabsystems iEMS Incubator/Shaker HT).

Thermostability was calculated as % residual activity as follows:

$\frac{{{{ABS}(340)}\mspace{11mu} {residual}} - {blank}}{{{{ABS}(340)}\mspace{11mu} {initial}} - {blank}} \times 100{\%.}$

The crude supernatant material was tested for remaining glucose in theculture medium after the growth period. Thermostability was notcalculated if remaining glucose was found in the culture medium. Basedon the residual activity of WT and mutant, the performance index (PI)for the thermostability was calculated. The PI of a variant is thequotient “Variant-residual activity/WT-residual activity.” The PI of WTis 1.0 and a variant with a PI>1.0 has a specific activity that isgreater than WT.

Data Analysis and Calculation of Performance Index of EthanolApplication Assay.

Protein levels were measured using a microfluidic electrophoresisinstrument (Caliper Life Sciences, Hopkinton, Mass., USA). Themicrofluidic chip and protein samples were prepared according to themanufacturer's instructions (LabChip® HT Protein Express, P/N 760301).Culture supernatants were prepared and stored in 96-well microtiterplates at −20° C. until use, when they were thawed by warming in a 37°C. incubator for 30 minutes. After shaking briefly, 2 μl of each culturesample was transferred to a 96-well PCR plate (Bio-Rad, Hercules,Calif., USA) containing 7 μl samples buffer (Caliper) followed byheating the plate to 90° C. for 5 minutes on a thermostaticallycontrolled plate heater. The plate was allowed to cool before adding 40μl water to each sample. The plate was placed in the instrument alongwith a protein standard supplied and calibrated by the manufacturer. Asthe proteins move past a focal point in the chip, the fluorescencesignal was recorded and the protein concentration was determined byquantitating the signal relative to the signal generated by thecalibrated set of protein standards.

After the Caliper protein determination the data was processed in thefollowing way. The calibration ladders were checked for correctness ofthe peak pattern. If the calibration ladder which was associated withthe run did not suffice, it was replaced by a calibration ladder of anadjacent run. For peak detection, the default settings of the globalpeak find option of the caliper software were used. The peak of interestwas selected at 75 kDA+/−10%.

The result was exported to a spreadsheet program and the peak area wasrelated to the corresponding activity (ABS340-blank measurement) in theethanol application assay. With the area and activity numbers of 12 WildType samples, a calibration line was made using the “Enzyme Kinetics”equation of the program Grafit Version 5 (Erithacus Software, Horley,UK) in combination with a non-linear fit function. The default settingswere used to calculate the Km and Vmax parameters. Based on these twoparameters, a Michaelis-Menten calibration curve was calculated and thespecific activity of each variant was calculated based on thecalibration curve.

Based on the specific activity of WT and variants the performance index(P) for the specific activity was calculated. The PI of a variant wascalculated as the quotient “Variant-specific activity/WT-specificactivity.” Using this quotient, the PI of WT is 1.0 and a variant with aPI>1.0 has a specific activity that is greater than WT.

Hexokinase Activity Assay:

Hexokinase cocktail: 10-15 minutes prior to use, 90 ml water was addedto a BoatIL container glucose HK R1 (IL test glucose (HK) kit,Instrument Laboratory #182507-40) and gently mixed. 100 μl of Hexokinasecocktail was added to 85 μl of dH₂O. 15 μl of sample was added to themixtures and incubated for 10 minutes in the dark at room temperature.Absorbance was read at 340 nm in a MTP-reader. Glucose concentrationswere calculated according to a glucose (0-2 mg/ml) standard curve.

Assay Conditions Ethanol Screening Assay:

8% stock solution: 8 g of soluble corn starch (Sigma #S4180) wassuspended in 40 ml dH₂O at room temperature. 50 ml of boiling dH₂O wasadded to the slurry in a 250 ml flask and cooked for 5 minutes. Thestarch solution was cooled to 25° C. and the volume adjusted to 100 mlwith dH₂O.

5 μl crude supernatant was diluted with 175 μl 50 mM NaAc buffer pH 4.5in a flat bottom 96-well MTP. 60 μl of this dilution was added to 120 μl4% soluble corn starch and incubated for 2 hrs at 32° C. 900 rpm(Thermolabsystems iEMS Incubator/Shaker HT). The reaction was stopped byadding 90 μl 4° C.-cold Stop Solution. The sample was placed on ice.Starch was spun down at 1118×g at 15° C. for 5 minutes (SIGMA 6K15) and15 μl supernatant was used in the Hexokinase activity assay describedabove to determine the glucose content. Stop solution (800 mMGlycine-NaOH buffer, pH 10). 4% (m/v) soluble starch working solution:stock solution was diluted (1:1) with 100 mM sodium acetate buffer pH3.7.

The crude supernatant material was tested for remaining glucose in theculture medium after the growth period. The amount of glucose producedby the glucoamylase was not calculated if remaining glucose was found inthe culture medium.

EXAMPLES

The following examples are provided in order to demonstrate and furtherillustrate certain embodiments and aspects of the present invention andare not to be construed as limiting the scope thereof.

Example 1 Construction of TrGA Site Evaluation Libraries (SELs) in thepTTT Vector for Expression in Trichoderma reesei

A Trichoderma reesei cDNA sequence (SEQ ID NO: 4) was cloned intopDONR™201 via the Gateway BP recombination reaction (Invitrogen,Carlsbad, Calif., USA) resulting in the entry vector pDONR-TrGA (FIG.2). The cDNA sequence (SEQ ID NO:4) encodes the TrGA signal peptide, theprosequence, and the mature protein, including the catalytic domain,linker region and starch binding domain (SEQ ID NO:1). SEQ ID NO:4 andSEQ ID NO:1 are shown in FIGS. 1B and 1A. FIG. 1C illustrates theprecursor and mature protein TrGA domains.

To express the TrGA protein in Trichoderma reesei, the TrGA codingsequence (SEQ ID NO:4) was cloned into the Gateway compatibledestination vector pTTT-Dest (FIG. 3) via the GATEWAY® LR recombinationreaction. The expression vector contained the T. reesei cbh1-derivedpromoter and terminator regions which allowed for strong inducibleexpression of a gene of interest. The vector also contained theAspergillus nidulans amdS selective marker which allowed for growth ofthe transformants on acetamide as a sole nitrogen source. The expressionvector also contained T. reesei telomere regions which allowed fornon-chromosomal plasmid maintenance in a fungal cell. On the destinationpTTT-Dest plasmid, the cbh1 promoter and terminator regions wereseparated by the chloramphenicol resistance gene, Cm^(R), and the lethalE. coli gene, ccdB, flanked by the bacteriophage lambda-based specificrecombination sites attR1, attR2. This configuration allowed for directselection of recombinants containing the TrGA gene under control of thecbh1 regulatory elements in the right orientation via the GATEWAY® LRrecombination reaction. The final expression vector pTTT-TrGA is shownin FIG. 4.

TrGA SELs were constructed using the pDONR-TrGA entry vector (FIG. 2) asa template and the primers listed in Table 1. All primers used in themutagenesis experiments contained the triplet NNS (N=A,C,T,G and S=C orG) at the position that aligns with the codon of the TrGA sequencedesigned to be mutated (SEQ ID NO:1), allowing for a randomincorporation of nucleotides at the preselected position. Constructionof each SEL started with two independent PCR amplifications on thepDONR-TrGA entry vector: one using the Gateway F (pDONR201-FW) and aspecific mutagenesis primer R (Table 2), and the other—the Gatewayprimer R (pDONR201-RV) and a specific mutagenesis primer F (Table 2).High fidelity PHUSION DNA polymerase (Finnzymes OY, Espoo, Finland) wasused in a PCR amplification reaction including 0.2 μM primers. Thereactions were carried out for 25 cycles according to the protocolprovided by Finnzymes. 1 μl aliquots of the PCR fragments obtained wereused as templates for a subsequent fusion PCR reaction together with theGateway FW and Gateway RV primers (Invitrogen). This PCR amplification,after 22 cycles, produced a population of the full-length linear TrGADNA fragments randomly mutated at the specific codon position. Thefragments were flanked by the Gateway-specific attL1, attL2recombination sites on both ends. The DNA fragments were purified with aCHARGESWITCH® PCR clean-up kit (Invitrogen, Carlsbad USA) and thenrecombined with 100 ng of the pTTT-destination vector (FIG. 3) using theLR CLONASE™ II enzyme mix according to the protocol supplied byInvitrogen. The recombination products that were generated weretransformed into E. coli Max Efficiency DH5α, as described by thesupplier (Invitrogen). The final expression constructs pTTT-TrGA withmutations at the desired position were selected by plating bacteria on2×YT agar plates (16 g/L Bacto Tryptone (Difco), 10 g/L Bacto YeastExtract (Difco), 5 g/L NaCl, 16 g/L Bacto Agar (Difco)) with 100 g/mlampicillin.

96 single colonies from each library were grown for 24 hrs at 37° C. inMTP containing 200 μL 2×YT medium with 100 μg/ml ampicillin. Cultureswere used directly to amplify PCR fragments encompassing the regionwhere a specific mutation was introduced. The specific PCR productsobtained were sequenced using an ABI3100 sequence analyzer (AppliedBiosystems). Each library contained from 15 to 19 different TrGAvariants in the final expression vector. These variants wereindividually transformed into T. reesei, as described below. Librariesare numbered from 1 to 182 referencing the specific amino acid residuein the TrGA sequence which was randomly mutated.

Table 1A and B—Primers Used to Generate TrGA SELs for the CatalyticDomain (Table 1A) and the Linker and Starch Binding Domain (Table 1B)(F=Forward; R=Reverse)

TABLE 1A catalytic domain primers AA- position F/R DNA Sequence 5′ to 3′pDON F TCGCGTTAACGCTAGCATGGATCTC (SEQ ID NO: 13) R201- pDON RTCGCGTTAACGCTAGCATGGATCTC (SEQ ID NO: 14) R201-   4 FCGTCACCAAGAGGTCTGTTGACNNSTTCATCAGCACCGAGACGCC (SEQ ID NO: 15)   4 RGTCAACAGACCTCTTGGTGACGTCG (SEQ ID NO: 16)   5 FCACCAAGAGGTCTGTTGACGACNNSATCAGCACCGAGACGCCTATTGC (SEQ ID NO: 17)   5 RGTCGTCAACAGACCTCTTGGTGAC (SEQ ID NO: 18)  10 FTGACGACTTCATCAGCACCGAGNNSCCTATTGCACTG (SEQ ID NO: 19)  10 RCTCGGTGCTGATGAAGTCGTC (SEQ ID NO: 20)  12 FTCATCAGCACCGAGACGCCTNNSGCACTGAACAATCTTCTTTGCA (SEQ ID NO: 21)  12 RAGGCGTCTCGGTGCTGATGAAGTCG (SEQ ID NO: 22)  14 FCAGCACCGAGACGCCTATTGCANNSAACAATCTTCTT (SEQ ID NO: 23)  14 RTGCAATAGGCGTCTCGGTGCT (SEQ ID NO: 24)  15 FCACCGAGACGCCTATTGCACTGNNSAATCTTCTTTGC (SEQ ID NO: 25)  15 RCAGTGCAATAGGCGTCTCGGT (SEQ ID NO: 26)  23 FCAATCTTCTTTGCAATGTTGGTNNSGATGGATGCCGT (SEQ ID NO: 27)  23 RACCAACATTGCAAAGAAGATTG (SEQ ID NO: 28)  24 FTTCTTTGCAATGTTGGTCCTNNSGGATGCCGTGCATTCGGCACAT (SEQ ID NO: 29)  24 RAGGACCAACATTGCAAAGAAGATTG (SEQ ID NO: 30)  29 FGTCCTGATGGATGCCGTGCANNSGGCACATCAGCTGGTGCGGTGA (SEQ ID NO: 31)  29 RTGCACGGCATCCATCAGGACCAACA (SEQ ID NO: 32)  42 FTGCGGTGATTGCATCTCCCAGCNNSATTGACCCGGAC (SEQ ID NO: 33)  42 RGCTGGGAGATGCAATCACCGCA (SEQ ID NO: 34)  43 FTGATTGCATCTCCCAGCACANNSGACCCGGACTACTATTACATGT (SEQ ID NO: 35)  43 RTGTGCTGGGAGATGCAATCACCGCA (SEQ ID NO: 36)  44 FTTGCATCTCCCAGCACAATTNNSCCGGACTACTATTACATGTGGA (SEQ ID NO: 37)  44 RAATTGTGCTGGGAGATGCAATCACC (SEQ ID NO: 38)  45 FCATCTCCCAGCACAATTGACNNSGACTACTATTACATGTGGACGC (SEQ ID NO: 39)  45 RGTCAATTGTGCTGGGAGATGCAATC (SEQ ID NO: 40)  46 FCTCCCAGCACAATTGACCCGNNSTACTATTACATGTGGACGCGAGA (SEQ ID NO: 41)  46 RCGGGTCAATTGTGCTGGGAGATGCA (SEQ ID NO: 42)  47 FCCAGCACAATTGACCCGGACNNSTATTACATGTGGACGCGAGATA (SEQ ID NO: 43)  47 RGTCCGGGTCAATTGTGCTGGGAGAT (SEQ ID NO: 44)  49 FCAATTGACCCGGACTACTATNNSATGTGGACGCGAGATAGCGCTC (SEQ ID NO: 45)  49 RATAGTAGTCCGGGTCAATTGTGCTG (SEQ ID NO: 46)  51 FACCCGGACTACTATTACATGNNSACGCGAGATAGCGCTCTTGTCT (SEQ ID NO: 47)  51 RCATGTAATAGTAGTCCGGGTCAATT (SEQ ID NO: 48)  59 FGACGCGAGATAGCGCTCTTGTCNNSAAGAACCTCATC (SEQ ID NO: 49)  59 RGACAAGAGCGCTATCTCGCGT (SEQ ID NO: 50)  60 FGCGAGATAGCGCTCTTGTCTTCNNSAACCTCATCGAC (SEQ ID NO: 51)  60 RGAAGACAAGAGCGCTATCTCG (SEQ ID NO: 52)  61 FAGATAGCGCTCTTGTCTTCAAGNNSCTCATCGACCGC (SEQ ID NO: 53)  61 RCTTGAAGACAAGAGCGCTATC (SEQ ID NO: 54)  65 FTGTCTTCAAGAACCTCATCGACNNSTTCACCGAAACG (SEQ ID NO: 55)  65 RGTCGATGAGGTTCTTGAAGAC (SEQ ID NO: 56)  67 FCAAGAACCTCATCGACCGCTTCNNSGAAACGTACGAT (SEQ ID NO: 57)  67 RGAAGCGGTCGATGAGGTTCTT (SEQ ID NO: 58)  68 FGAACCTCATCGACCGCTTCACCNNSACGTACGATGCG (SEQ ID NO: 59)  68 RGGTGAAGCGGTCGATGAGGTT (SEQ ID NO: 60)  70 FTCGACCGCTTCACCGAAACGNNSGATGCGGGCCTGCAGCGCCGCA (SEQ ID NO: 61)  70 RCGTTTCGGTGAAGCGGTCGATGAGG (SEQ ID NO: 62)  72 FCCGCTTCACCGAAACGTACGATNNSGGCCTGCAGCGC (SEQ ID NO: 63)  72 RATCGTACGTTTCGGTGAAGCGG (SEQ ID NO: 64)  73 FCTTCACCGAAACGTACGATGCGNNSCTGCAGCGCCGC (SEQ ID NO: 65)  73 RCGCATCGTACGTTTCGGTGAA (SEQ ID NO: 66)  75 FAAACGTACGATGCGGGCCTGNNSCGCCGCATCGAGCAGTACATTA (SEQ ID NO: 67)  75 RCAGGCCCGCATCGTACGTTTCGGTG (SEQ ID NO: 68)  76 FCGTACGATGCGGGCCTGCAGNNSCGCATCGAGCAGTACATTACTG (SEQ ID NO: 69)  76 RCTGCAGGCCCGCATCGTACGTTTCG (SEQ ID NO: 70)  94 FCTCTCCAGGGCCTCTCTAACNNSTCGGGCTCCCTCGCGGACGGCT (SEQ ID NO: 71)  94 RGTTAGAGAGGCCCTGGAGAGTGACC (SEQ ID NO: 72)  97 FGGGCCTCTCTAACCCCTCGGGCNNSCTCGCGGACGGC (SEQ ID NO: 73)  97 RGCCCGAGGGGTTAGAGAGGCC (SEQ ID NO: 74)  98 FCCTCTCTAACCCCTCGGGCTCCNNSGCGGACGGCTCT (SEQ ID NO: 75)  98 RGGAGCCCGAGGGGTTAGAGAG (SEQ ID NO: 76)  99 FCTCTAACCCCTCGGGCTCCCTCNNSGACGGCTCTGGT (SEQ ID NO: 77)  99 RGAGGGAGCCCGAGGGGTTAGA (SEQ ID NO: 78) 100 FACCCCTCGGGCTCCCTCGCGNNSGGCTCTGGTCTCGGCGAGCCCA (SEQ ID NO: 79) 100 RCGCGAGGGAGCCCGAGGGGTTAGAG (SEQ ID NO: 80) 102 FCTCGGGCTCCCTCGCGGACGGCNNSGGTCTCGGCGAG (SEQ ID NO: 81) 102 RGCCGTCCGCGAGGGAGCCCGA (SEQ ID NO: 82) 110 FTGGTCTCGGCGAGCCCAAGTTTNNSTTGACCCTGAAG (SEQ ID NO: 83) 110 RAAACTTGGGCTCGCCGAGACCA (SEQ ID NO: 84) 111 FTCTCGGCGAGCCCAAGTTTGAGNNSACCCTGAAGCCT (SEQ ID NO: 85) 111 RCTCAAACTTGGGCTCGCCGAG (SEQ ID NO: 86) 113 FCGAGCCCAAGTTTGAGTTGACCNNSAAGCCTTTCACC (SEQ ID NO: 87) 113 RGGTCAACTCAAACTTGGGCTC (SEQ ID NO: 88) 114 FCCAAGTTTGAGTTGACCCTGNNSCCTTTCACCGGCAACTGGGGTC (SEQ ID NO: 89) 114 RCAGGGTCAACTCAAACTTGGGCTCG (SEQ ID NO: 90) 116 FTTGAGTTGACCCTGAAGCCTNNSACCGGCAACTGGGGTCGACCGCA (SEQ ID NO: 91) 116 RAGGCTTCAGGGTCAACTCAAACTTG (SEQ ID NO: 92) 119 FCCCTGAAGCCTTTCACCGGCNNSTGGGGTCGACCGCAGCGGGATG (SEQ ID NO: 93) 119 RGCCGGTGAAAGGCTTCAGGGTCAAC (SEQ ID NO: 94) 122 FCTTTCACCGGCAACTGGGGTNNSCCGCAGCGGGATGGCCCAGCTC (SEQ ID NO: 95) 122 RACCCCAGTTGCCGGTGAAAGGCTTC (SEQ ID NO: 96) 125 FGCAACTGGGGTCGACCGCAGNNSGATGGCCCAGCTCTGCGAGCCA (SEQ ID NO: 97) 125 RCTGCGGTCGACCCCAGTTGCCGGTG (SEQ ID NO: 98) 133 FGGATGGCCCAGCTCTGCGAGCCNNSGCCTTGATTGGA (SEQ ID NO: 99) 133 RGGCTCGCAGAGCTGGGCCATCC (SEQ ID NO: 100) 137 FTGCGAGCCATTGCCTTGATTNNSTACTCAAAGTGGCTCATCAACA (SEQ ID NO: 101) 137 RAATCAAGGCAATGGCTCGCAGAGCT (SEQ ID NO: 102) 140 FCATTGCCTTGATTGGATACTCANNSTGGCTCATCAAC (SEQ ID NO: 103) 140 RTGAGTATCCAATCAAGGCAATG (SEQ ID NO: 104) 144 FTGGATACTCAAAGTGGCTCATCNNSAACAACTATCAG (SEQ ID NO: 105) 144 RGATGAGCCACTTTGAGTATCC (SEQ ID NO: 106) 145 FATACTCAAAGTGGCTCATCAACNNSAACTATCAGTCG (SEQ ID NO: 107) 145 RGTTGATGAGCCACTTTGAGTA (SEQ ID NO: 108) 146 FCAAAGTGGCTCATCAACAACNNSTATCAGTCGACTGTGTCCAACG (SEQ ID NO: 109) 146 RGTTGTTGATGAGCCACTTTGAGTAT (SEQ ID NO: 110) 147 FAAAGTGGCTCATCAACAACAACNNSCAGTCGACTGTG (SEQ ID NO: 111) 147 RGTTGTTGTTGATGAGCCACTT (SEQ ID NO: 112) 148 FGGCTCATCAACAACAACTATNNSTCGACTGTGTCCAACGTCATCT (SEQ ID NO: 113) 148 RATAGTTGTTGTTGATGAGCCACTTT (SEQ ID NO: 114) 152 FCAACAACTATCAGTCGACTGTGNNSAACGTCATCTGG (SEQ ID NO: 115) 152 RCACAGTCGACTGATAGTTGTT (SEQ ID NO: 116) 153 FCAACTATCAGTCGACTGTGTCCNNSGTCATCTGGCCT (SEQ ID NO: 117) 153 RGGACACAGTCGACTGATAGTT (SEQ ID NO: 118) 164 FGCCTATTGTGCGCAACGACCTCNNSTATGTTGCCCAGT (SEQ ID NO: 119) 164 RGAGGTCGTTGCGCACAATAGG (SEQ ID NO: 120) 169 FACCTCAACTATGTTGCCCAGNNSTGGAACCAAACCGGCTTTGACC (SEQ ID NO: 121) 169 RCTGGGCAACATAGTTGAGGTCGTTG (SEQ ID NO: 122) 172 FATGTTGCCCAGTACTGGAACNNSACCGGCTTTGACCTCTGGGAAG (SEQ ID NO: 123) 172 RGTTCCAGTACTGGGCAACATAGTTG (SEQ ID NO: 124) 175 FAGTACTGGAACCAAACCGGCNNSGACCTCTGGGAAGAAGTCAATG (SEQ ID NO: 125) 175 RGCCGGTTTGGTTCCAGTACTGGGCA (SEQ ID NO: 126) 178 FACCAAACCGGCTTTGACCTCNNSGAAGAAGTCAATGGGAGCTCAT (SEQ ID NO: 127) 178 RGAGGTCAAAGCCGGTTTGGTTCCAG (SEQ ID NO: 128) 180 FCCGGCTTTGACCTCTGGGAANNSGTCAATGGGAGCTCATTCTTTA (SEQ ID NO: 129) 180 RTTCCCAGAGGTCAAAGCCGGTTTGG (SEQ ID NO: 130) 181 FGCTTTGACCTCTGGGAAGAANNSAATGGGAGCTCATTCTTTACTG (SEQ ID NO: 131) 181 RTTCTTCCCAGAGGTCAAAGCCGGTT (SEQ ID NO: 132) 182 FCTTTGACCTCTGGGAAGAAGTCNNSGGGAGCTCATTC (SEQ ID NO: 133) 182 RGACTTCTTCCCAGAGGTCAAAG (SEQ ID NO: 134) 204 FTGTCGAGGGCGCCACTCTTGCTNNSACTCTTGGCCAG (SEQ ID NO: 135) 204 RAGCAAGAGTGGCGCCCTCGAC (SEQ ID NO: 136) 205 FCGAGGGCGCCACTCTTGCTGCCNNSCTTGGCCAGTCG (SEQ ID NO: 137) 205 RGGCAGCAAGAGTGGCGCCCTC (SEQ ID NO: 138) 208 FCTCTTGCTGCCACTCTTGGCNNSTCGGGAAGCGCTTATTCATCTG (SEQ ID NO: 139) 208 RGCCAAGAGTGGCAGCAAGAGTGGCG (SEQ ID NO: 140) 211 FCCACTCTTGGCCAGTCGGGANNSGCTTATTCATCTGTTGCTCCCC (SEQ ID NO: 141) 211 RTCCCGACTGGCCAAGAGTGGCAGCA (SEQ ID NO: 142) 214 FTGGCCAGTCGGGAAGCGCTTATNNSTCTGTTGCTCCC (SEQ ID NO: 143) 214 RATAAGCGCTTCCCGACTGGCC (SEQ ID NO: 144) 216 FGTCGGGAAGCGCTTATTCATCTNNSGCTCCCCAGGTT (SEQ ID NO: 145) 216 RAGATGAATAAGCGCTTCCCGA (SEQ ID NO: 146) 219 FCGCTTATTCATCTGTTGCTCCCNNSGTTTTGTGCTTT (SEQ ID NO: 147) 219 RGGGAGCAACAGATGAATAAGC (SEQ ID NO: 148) 228 FTGTGCTTTCTCCAACGATTCNNSGTGTCGTCTGGTGGATACGTCG (SEQ ID NO: 149) 228 RGAATCGTTGGAGAAAGCACAAAACCT (SEQ ID NO: 150) 229 FGTGCTTTCTCCAACGATTCTGGNNSTCGTCTGGTGGA (SEQ ID NO: 151) 229 RCCAGAATCGTTGGAGAAAGCA (SEQ ID NO: 152) 230 FCTTTCTCCAACGATTCTGGGTGNNSTCTGGTGGATACG (SEQ ID NO: 153) 230 RCACCCAGAATCGTTGGAGAAA (SEQ ID NO: 154) 231 FTCTCCAACGATUCTGGGTGTCGNNSGGTGGATACGTC (SEQ ID NO: 155) 231 RCGACACCCAGAATCGTTGGAGA (SEQ ID NO: 156) 236 FGGTGTCGTCTGGTGGATACGTCNNSTCCAACATCAACAC (SEQ ID NO: 157) 236 RGACGTATCCACCAGACGACAC (SEQ ID NO: 158) 239 FTGGTGGATACGTCGACTCCAACNNSAACACCAACGAG (SEQ ID NO: 159) 239 RGTTGGAGTCGACGTATCCACC (SEQ ID NO: 160) 240 FTGGATACGTCGACTCCAACATCNNSACCAACGAGGGCA (SEQ ID NO: 161) 240 RGATGTTGGAGTCGACGTATCCA (SEQ ID NO: 162) 241 FATACGTCGACTCCAACATCAACNNSAACGAGGGCAGGAC (SEQ ID NO: 163) 241 RGTTGATGTTGGAGTCGACGTA (SEQ ID NO: 164) 242 FTCGACTCCAACATCAACACCNNSGAGGGCAGGACTGGCAAGGATG (SEQ ID NO: 165) 242 RGGTGTTGATGTTGGAGTCGACGTAT (SEQ ID NO: 166) 243 FACTCCAACATCAACACCAACNNSGGCAGGACTGGCAAGGATGTCA (SEQ ID NO: 167) 243 RGTTGGTGTTGATGTTGGAGTCGACG (SEQ ID NO: 168) 244 FCTCCAACATCAACACCAACGAGNNSAGGACTGGCAAG (SEQ ID NO: 169) 244 RCTCGTTGGTGTTGATGTTGGAGT (SEQ ID NO: 170) 245 FACATCAACACCAACGAGGGCNNSACTGGCAAGGATGTCAACTCCG (SEQ ID NO: 171) 245 RGCCCTCGTTGGTGTTGATGTTGGAGT (SEQ ID NO: 172) 263 FTTCCATCCACACCTTCGATCCCNNSCTTGGCTGTGAC (SEQ ID NO: 173) 263 RGGGATCGAAGGTGTGGATGGA (SEQ ID NO: 174) 264 FCATCCACACCTTCGATCCCAACNNSGGCTGTGACGCA (SEQ ID NO: 175) 264 RGTTGGGATCGAAGGTGTGGAT (SEQ ID NO: 176) 265 FCCACACCTTCGATCCCAACCTTNNSTGTGACGCAGGC (SEQ ID NO: 177) 265 RAAGGTTGGGATCGAAGGTGTG (SEQ ID NO: 178) 268 FCGATCCCAACCTTGGCTGTGACNNSGGCACCTTCCAGC (SEQ ID NO: 179) 268 RGTCACAGCCAAGGTTGGGATC (SEQ ID NO: 180) 269 FTCCCAACCTTGGCTGTGACGCANNSACCTTCCAGCCA (SEQ ID NO: 181) 269 RTGCGTCACAGCCAAGGTTGGG (SEQ ID NO: 182) 276 FAGGCACCTTCCAGCCATGCAGTNNSAAAGCGCTCTCC (SEQ ID NO: 183) 276 RACTGCATGGCTGGAAGGTGCC (SEQ ID NO: 184) 284 FCAAAGCGCTCTCCAACCTCAAGNNSGTTGTCGACTCCT (SEQ ID NO: 185) 284 RCTTGAGGTTGGAGAGCGCTTT (SEQ ID NO: 186) 291 FGGTTGTTGTCGACTCCTTCCGCNNSATCTACGGCGTG (SEQ ID NO: 187) 291 RGCGGAAGGAGTCGACAACAAC (SEQ ID NO: 188) 292 FTTGTCGACTCCTTCCGCTCCNNSTACGGCGTGAACAAGGGCATTC (SEQ ID NO: 189) 292 RGGAGCGGAAGGAGTCGACAACAACC (SEQ ID NO: 190) 294 FACTCCTTCCGCTCCATCTACNNSGTGAACAAGGGCATTCCTGCCG (SEQ ID NO: 191) 294 RGTAGATGGAGCGGAAGGAGTCGACA (SEQ ID NO: 192) 297 FGCTCCATCTACGGCGTGAACNNSGGCATTCCTGCCGGTGCTGCCG (SEQ ID NO: 193) 297 RGTTCACGCCGTAGATGGAGCGGAAG (SEQ ID NO: 194) 300 FCTACGGCGTGAACAAGGGCATTNNSGCCGGTGCTGCCG (SEQ ID NO: 195) 300 RAATGCCCTTGTTCACGCCGTA (SEQ ID NO: 196) 301 FCGGCGTGAACAAGGGCATTCCTNNSGGTGCTGCCGTC (SEQ LD NO: 197) 301 RAGGAATGCCCTTGTTCACGCC (SEQ ID NO: 198) 303 FGAACAAGGGCATTCCTGCCGGTNNSGCCGTCGCCATT (SEQ ID NO: 199) 303 RACCGGCAGGAATGCCCTTGTT (SEQ ID NO: 200) 309 FGTGCTGCCGTCGCCATTGGCNNSTATGCAGAGGATGTGTACTACA (SEQ ID NO: 201) 309 RGCCAATGGCGACGGCAGCACCGGCA (SEQ ID NO: 202) 310 FCTGCCGTCGCCATTGGCCGGNNSGCAGAGGATGTGTACTACAACG (SEQ ID NO: 203) 310 RCCGGCCAATGGCGACGGCAGCACCG (SEQ ID NO: 204) 311 FTGCCGTCGCCATTGGCCGGTATNNSGAGGATGTGTAC (SEQ ID NO: 205) 311 RATACCGGCCAATGGCGACGGC (SEQ ID NO: 206) 313 FCCATTGGCCGGTATGCAGAGNNSGTGTACTACAACGGCAACCCTT (SEQ ID NO: 207) 313 FCCATTGGCCGGTATGCAGAGNNSGTGTACTACAACGGCAACCCTT (SEQ ID NO: 208) 313 RCTCTGCATACCGGCCAATGGCGACG (SEQ ID NO: 209) 313 RCTCTGCATACCGGCCAATGGCGACG (SEQ ID NO: 210) 314 FTTGGCCGGTATGCAGAGGATNNSTACTACAACGGCAACCCTTGGT (SEQ ID NO: 211) 314 RATCCTCTGCATACCGGCCAATGGCG (SEQ ID NO: 212) 315 FGCCGGTATGCAGAGGATGTGNNSTACAACGGCAACCCTTGGTATC (SEQ ID NO: 213) 315 RCACATCCTCTGCATACCGGCCAATG (SEQ ID NO: 214) 316 FGGTATGCAGAGGATGTGTACNNSAACGGCAACCCTTGGTATCTTG (SEQ ID NO: 215) 316 RGTACACATCCTCTGCATACCGGCCAAT (SEQ ID NO: 216) 317 FATGCAGAGGATGTGTACTACNNSGGCAACCCTTGGTATCTTGCTA (SEQ ID NO: 217) 317 FATGCAGAGGATGTGTACTACNNSGGCAACCCTTGGTATCTTGCTA (SEQ ID NO: 218) 317 RGTAGTACACATCCTCTGCATACCGGC (SEQ ID NO: 219) 317 RGTAGTACACATCCTCTGCATACCGGC (SEQ ID NO: 220) 321 FTGTACTACAACGGCAACCCTNNSTATCTTGCTACATTTGCTGCTG (SEQ ID NO: 221) 321 FTGTACTACAACGGCAACCCTNNSTATCTTGCTACATTTGCTGCTG (SEQ ID NO: 222) 321 RAGGGTTGCCGTTGTAGTACACATCC (SEQ ID NO: 223) 321 RAGGGTTGCCGTTGTAGTACACATCC (SEQ ID NO: 224) 338 FGCAGCTGTACGATGCCATCTACNNSTGGAAGAAGACG (SEQ ID NO: 225) 338 RGTAGATGGCATCGTACAGCTG (SEQ ID NO: 226) 340 FACGATGCCATCTACGTCTGGNNSAAGACGGGCTCCATCACGGTGA (SEQ ID NO: 227) 340 RCCAGACGTAGATGGCATCGTACAGC (SEQ ID NO: 228) 341 FATGCCATCTACGTCTGGAAGNNSACGGGCTCCATCACGGTGACCG (SEQ ID NO: 229) 341 RCTTCCAGACGTAGATGGCATCGTACAGC (SEQ ID NO: 230) 342 FATGCCATCTACGTCTGGAAGAAGNNSGGCTCCATCACG (SEQ ID NO: 231) 342 RCTTCTTCCAGACGTAGATGGC (SEQ ID NO: 232) 344 FCTACGTCTGGAAGAAGACGGGCNNSATCACGGTGACC (SEQ ID NO: 233) 344 RGCCCGTCTTCTTCCAGACGTAG (SEQ ID NO: 234) 346 FCTGGAAGAAGACGGGCTCCATCNNSGTGACCGCCACCTC (SEQ ID NO: 235) 346 RGATGGAGCCCGTCTTCTTCCA (SEQ ID NO: 236) 349 FGACGGGCTCCATCACGGTGACCNNSACCTCCCTGGCC (SEQ ID NO: 237) 349 RGGTCACCGTGATGGAGCCCGT (SEQ ID NO: 238) 350 FGCTCCATCACGGTGACCGCCNNSTCCCTGGCCTTCTTCCAGGAGC (SEQ ID NO: 239) 350 RGGCGGTCACCGTGATGGAGCCCGTC (SEQ ID NO: 240) 356 FCCACCTCCCTGGCCTTCTTCNNSGAGCTTGTTCCTGGCGTGACGG (SEQ ID NO: 241) 356 RGAAGAAGGCCAGGGAGGTGGCGGTC (SEQ ID NO: 242) 359 FCCTGGCCTTCTTCCAGGAGCTTNNSCCTGGCGTGACG (SEQ ID NO: 243) 359 RAAGCTCCTGGAAGAAGGCCAG (SEQ ID NO: 244) 361 FCTTCTTCCAGGAGCTTGTTCCTNNSGTGACGGCCGGG (SEQ ID NO: 245) 361 RAGGAACAAGCTCCTGGAAGAA (SEQ ID NO: 246) 363 FAGGAGCTTGTTCCTGGCGTGNNSGCCGGGACCTACTCCAGCAGCT (SEQ ID NO: 247) 363 RCACGCCAGGAACAAGCTCCTGGAAG (SEQ ID NO: 248) 364 FGGAGCTTGTTCCTGGCGTGACGNNSGGGACCTACTCC (SEQ ID NO: 249) 364 RCGTCACGCCAGGAACAAGCTC (SEQ ID NO: 250) 368 FGCGTGACGGCCGGGACCTACNNSAGCAGCTCTTCGACCTTTACCA (SEQ ID NO: 251) 368 RGTAGGTCCCGGCCGTCACGCCAGGA (SEQ ID NO: 252) 369 FTGACGGCCGGGACCTACTCCNNSAGCTCTTCGACCTTTACCAACA (SEQ ID NO: 253) 369 RGGAGTAGGTCCCGGCCGTCACGCCA (SEQ ID NO: 254) 375 FCTCCAGCAGCTCTTCGACCTTTNNSAACATCATCAACG (SEQ ID NO: 255) 375 RAAAGGTCGAAGAGCTGCTGGA (SEQ ID NO: 256) 376 FGCAGCTCTTCGACCTTTACCNNSATCATCAACGCCGTCTCGACAT (SEQ ID NO: 257) 376 RGGTAAAGGTCGAAGAGCTGCTGGAG (SEQ ID NO: 258) 379 FTTCGACCTTTACCAACATCATCNNSGCCGTCTCGACA (SEQ ID NO: 259) 379 RGATGATGTTGGTAAAGGTCGA (SEQ ID NO: 260) 382 FTACCAACATCATCAACGCCGTCNNSACATACGCCGAT (SEQ ID NO: 261) 382 RGACGGCGTTGATGATGTTGGT (SEQ ID NO: 262) 390 FGACATACGCCGATGGCTTCCTCNNSGAGGCTGCCAAG (SEQ ID NO: 263) 390 RGAGGAAGCCATCGGCGTATGT (SEQ ID NO: 264) 391 FATACGCCGATGGCTTCCTCAGCNNSGCTGCCAAGTAC (SEQ ID NO: 265) 391 RGCTGAGGAAGCCATCGGCGTA (SEQ ID NO: 266) 393 FCGATGGCTTCCTCAGCGAGGCTNNSAAGTACGTCCCC (SEQ ID NO: 267) 393 RAGCCTCGCTGAGGAAGCCATC (SEQ ID NO: 268) 394 FTGGCTTCCTCAGCGAGGCTGCCNNSTACGTCCCCGCC (SEQ ID NO: 269) 394 RGGCAGCCTCGCTGAGGAAGCC (SEQ ID NO: 270) 395 FTCCTCAGCGAGGCTGCCAAGNNSGTCCCCGCCGACGGTTCGCTGG (SEQ ID NO: 271) 395 RCTTGGCAGCCTCGCTGAGGAAGCCA (SEQ ID NO: 272) 398 FAGGCTGCCAAGTACGTCCCCNNSGACGGTTCGCTGGCCGAGCAGTT (SEQ ID NO: 273) 398 RGGGGACGTACTTGGCAGCCTCGCTG (SEQ ID NO: 274) 401 FAGTACGTCCCCGCCGACGGTNNSCTGGCCGAGCAGTTTGACCGCA (SEQ ID NO: 275) 401 RACCGTCGGCGGGGACGTACTTGGCAG (SEQ ID NO: 276) 408 FCGCTGGCCGAGCAGTTTGACNNSAACAGCGGCACTCCGCTGTCTG (SEQ ID NO: 277) 408 RGTCAAACTGCTCGGCCAGCGAACCG (SEQ ID NO: 278) 409 FTGGCCGAGCAGTTTGACCGCNNSAGCGGCACTCCGCTGTCTGCGC (SEQ ID NO: 279) 409 RGCGGTCAAACTGCTCGGCCAGCGAA (SEQ ID NO: 280) 410 FGGCCGAGCAGTTTGACCGCAACNNSGGCACTCCGCTG (SEQ ID NO: 281) 410 RGTTGCGGTCAAACTGCTCGGC (SEQ ID NO: 282) 412 FAGTTTGACCGCAACAGCGGCNNSCCGCTGTCTGCGCTTCACCTGA (SEQ ID NO: 283) 412 RGCCGCTGTTGCGGTCAAACTGCTCG (SEQ ID NO: 284) 415 FGCAACAGCGGCACTCCGCTGNNSGCGCTTCACCTGACGTGGTCGT (SEQ ID NO: 285) 415 RCAGCGGAGTGCCGCTGTTGCGGTCA (SEQ ID NO: 286) 417 FCAGCGGCACTCCGCTGTCTGCGNNSCACCTGACGTGGT (SEQ ID NO: 287) 417 RCGCAGACAGCGGAGTGCCGCT (SEQ ID NO: 288) 418 FGCACTCCGCTGTCTGCGCTTNNSCTGACGTGGTCGTACGCCTCGT (SEQ ID NO: 289) 418 RAAGCGCAGACAGCGGAGTGCCGCTG (SEQ ID NO: 290) 421 FTGTCTGCGCTTCACCTGACGNNSTCGTACGCCTCGTTCTTGACAG (SEQ ID NO: 291) 421 RCGTCAGGTGAAGCGCAGACAGCGGA (SEQ ID NO: 292) 430 FGTACGCCTCGTTCTTGACAGCCNNSGCCCGTCGGGCT (SEQ ID NO: 293) 430 RGGCTGTCAAGAACGAGGCGTA (SEQ ID NO: 294) 431 FCGCCTCGTTCTTGACAGCCACGNNSCGTCGGGCTGGC (SEQ ID NO: 295) 431 RCGTGGCTGTCAAGAACGAGGC (SEQ ID NO: 296) 433 FTCTTGACAGCCACGGCCCGTNNSGCTGGCATCGTGCCCCCCTCGT (SEQ ID NO: 297) 433 RACGGGCCGTGGCTGTCAAGAACGAG (SEQ ID NO: 298) 436 FCCACGGCCCGTCGGGCTGGCNNSGTGCCCCCCTCGTGGGCCAACA (SEQ ID NO: 299) 436 RGCCAGCCCGACGGGCCGTGGCTGTC (SEQ ID NO: 300) 442 FTGGCATCGTGCCCCCCTCGTGGNNSAACAGCAGCGCT (SEQ ID NO: 301) 442 RCCACGAGGGGGGCACGATGCC (SEQ ID NO: 302) 443 FCATCGTGCCCCCCTCGTGGGCCNNSAGCAGCGCTAGC (SEQ ID NO: 303) 443 RGGCCCACGAGGGGGGCACGAT (SEQ ID NO: 304) 444 FCGTGCCCCCCTCGTGGGCCAACNNSAGCGCTAGCACG (SEQ ID NO: 305) 444 RGTTGGCCCACGAGGGGGGCAC (SEQ ID NO: 306) 448 FGTGGGCCAACAGCAGCGCTAGCNNSATCCCCTCGACG (SEQ ID NO: 307)

TABLE 1B Linker and SBD primers AA- position F/R DNA sequence 5′ to 3′451 F GCAGCGCTAGCACGATCCCCNNSACGTGCTCCGGCGCGTCCGTGG (SEQ ID NO: 308) 451R GGGGATCGTGCTAGCGCTGCTGTTG (SEQ ID NO: 309) 493 FCTACACGCCCCTGCCCTGCGCGNNSCCAACCTCCGTG (SEQ ID NO: 310) 493 RCGCGCAGGGCAGGGGCGTGTA (SEQ ID NO: 311) 494 FCACGCCCCTGCCCTGCGCGACCNNSACCTCCGTGGCC (SEQ ID NO: 312) 494 RGGTCGCGCAGGGCAGGGGCGT (SEQ ID NO: 313) 495 FGCCCCTGCCCTGCGCGACCCCANNSTCCGTGGCCGTC (SEQ ID NO: 314) 495 RTGGGGTCGCGCAGGGCAGGGG (SEQ ID NO: 315) 501 FCCCAACCTCCGTGGCCGTCACCNNSCACGAGCTCGTGT (SEQ ID NO: 316) 501 RGGTGACGGCCACGGAGGTTGG (SEQ ID NO: 317) 502 FAACCTCCGTGGCCGTCACCTTCNNSGAGCTCGTGTCG (SEQ ID NO: 318) 502 RGAAGGTGACGGCCACGGAGGT (SEQ ID NO: 319) 503 FCTCCGTGGCCGTCACCTTCCACNNSCTCGTGTCGACACA (SEQ ID NO: 320) 503 RGTGGAAGGTGACGGCCACGGA (SEQ ID NO: 321) 508 FCTTCCACGAGCTCGTGTCGACANNSTTTGGCCAGACG (SEQ ID NO: 322) 508 RTGTCGACACGAGCTCGTGGAA (SEQ ID NO: 323) 511 FGCTCGTGTCGACACAGTTTGGCNNSACGGTCAAGGTG (SEQ ID NO: 324) 511 RGCCAAACTGTGTCGACACGAG (SEQ ID NO: 325) 514 FCACAGTTTGGCCAGACGGTCNNSGTGGCGGGCAACGCCGCGGCCC (SEQ ID NO: 326) 514 RGACCGTCTGGCCAAACTGTGTCGAC (SEQ ID NO: 327) 517 FTGGCCAGACGGTCAAGGTGGCGNNSAACGCCGCGGCCCTGGG (SEQ ID NO: 328) 517 RCGCCACCTTGACCGTCTGGCCAAACTG (SEQ ID NO: 329) 518 FCCAGACGGTCAAGGTGGCGGGCNNSGCCGCGGCCCTGGGCAACT (SEQ ID NO: 330) 518 RGCCCGCCACCTTGACCGTCTGGCCAAA (SEQ ID NO: 331) 519 FGACGGTCAAGGTGGCGGGCAACNNSGCGGCCCTGGGCAACT (SEQ ID NO: 332) 519 RGTTGCCCGCCACCTTGACCGTCTGGCC (SEQ ID NO: 333) 520 FGGTCAAGGTGGCGGGCAACGCCNNSGCCCTGGGCAACTGGA (SEQ ID NO: 334) 520 RGGCGTTGCCCGCCACCTTGACCGTCTG (SEQ ID NO: 335) 525 FCAACGCCGCGGCCCTGGGCAACNNSAGCACGAGCGCCGCCG (SEQ ID NO: 336) 525 RGTTGCCCAGGGCCGCGGCGTTGCCCGC (SEQ ID NO: 337) 527 FCGCGGCCCTGGGCAACTGGAGCNNSAGCGCCGCCGTGGCTC (SEQ ID NO: 338) 527 RGCTCCAGTTGCCCAGGGCCGCGGCGTT (SEQ ID NO: 339) 531 FCAACTGGAGCACGAGCGCCGCCNNSGCTCTGGACGCCGTCA (SEQ ID NO: 340) 531 RGGCGGCGCTCGTGCTCCAGTTGCCCAG (SEQ ID NO: 341) 533 FGAGCACGAGCGCCGCCGTGGCTNNSGACGCCGTCAACTATGC (SEQ ID NO: 342) 533 RAGCCACGGCGGCGCTCGTGCTCCAGTT (SEQ ID NO: 343) 535 FGAGCGCCGCCGTGGCTCTGGACNNSGTCAACTATGCCGATA (SEQ ID NO: 344) 535 RGTCCAGAGCCACGGCGGCGCTCGTGCT (SEQ ID NO: 345) 536 FCGCCGCCGTGGCTCTGGACGCCNNSAACTATGCCGATAACC (SEQ ID NO: 346) 536 RGGCGTCCAGAGCCACGGCGGCGCTCGT (SEQ ID NO: 347) 537 FCGCCGTGGCTCTGGACGCCGTCNNSTATGCCGATAAC (SEQ ID NO: 348) 537 FCGCCGTGGCTCTGGACGCCGTCNNSTATGCCGATAACCACCCC (SEQ ID NO: 349) 537 RGACGGCGTCCAGAGCCACGGCGGCGCT (SEQ ID NO: 350) 537 RGACGGCGTCCAGAGCCACGGCGGCGCT (SEQ ID NO: 351) 538 FCGTGGCTCTGGACGCCGTCAACNNSGCCGATAACCACCCCC (SEQ ID NO: 352) 538 RGTTGACGGCGTCCAGAGCCACGGCGGCG (SEQ ID NO: 353) 539 FGGCTCTGGACGCCGTCAACTATNNSGATAACCACCCCCTGT (SEQ ID NO: 354) 539 RATAGTTGACGGCGTCCAGAGCCACGGC (SEQ ID NO: 355) 540 FTCTGGACGCCGTCAACTATGCCNNSAACCACCCCCTGTGGATT (SEQ ID NO: 356) 540 RGGCATAGTTGACGGCGTCCAGAGCCAC (SEQ ID NO: 357) 541 FGGACGCCGTCAACTATGCCGATNNSCACCCCCTGTGGATTGGG (SEQ ID NO: 358) 541 RATCGGCATAGTTGACGGCGTCCAGAGC (SEQ ID NO: 359) 545 FCTATGCCGATAACCACCCCCTGNNSATTGGGACGGTCAACCTC (SEQ ID NO: 360) 545 RCAGGGGGTGGTTATCGGCATAGTTGAC (SEQ ID NO: 361) 546 FTGCCGATAACCACCCCCTGTGGNNSGGGACGGTCAACCTCGAG (SEQ ID NO: 362) 546 RCCACAGGGGGTGGTTATCGGCATAGTT (SEQ ID NO: 363) 547 FCGATAACCACCCCCTGTGGATTNNSACGGTCAACCTCGAGGCT (SEQ ID NO: 364) 547 RAATCCACAGGGGGTGGTTATCGGCATA (SEQ ID NO: 365) 549 FCCACCCCCTGTGGATTGGGACGNNSAACCTCGAGGCTGGAGAC (SEQ ID NO: 366) 549 RCGTCCCAATCCACAGGGGGTGGTTATC (SEQ ID NO: 367) 551 FCCTGTGGATTGGGACGGTCAACNNSGAGGCTGGAGACGTCGTG (SEQ ID NO: 368) 551 RGTTGACCGTCCCAATCCACAGGGGGTG (SEQ ID NO: 369) 561 FTGGAGACGTCGTGGAGTACAAGNNSATCAATGTGGGCCAAGAT (SEQ ID NO: 370) 561 RCTTGTACTCCACGACGTCTCCAGCCTC (SEQ ID NO: 371) 563 FCGTCGTGGAGTACAAGTACATCNNSGTGGGCCAAGATGGCTCC (SEQ ID NO: 372) 563 RGATGTACTTGTACTCCACGACGTCTCC (SEQ ID NO: 373) 567 FCAAGTACATCAATGTGGGCCAANNSGGCTCCGTGACCTGGGAG (SEQ ID NO: 374) 567 RTTGGCCCACATTGATGTACTTGTACTC (SEQ ID NO: 375) 569 FCATCAATGTGGGCCAAGATGGCNNSGTGACCTGGGAGAGTGAT (SEQ ID NO: 376) 569 RGCCATCTTGGCCCACATTGATGTACTTG (SEQ ID NO: 377) 577 FCGTGACCTGGGAGAGTGATCCCNNSCACACTTACACGGTTCCT (SEQ ID NO: 378) 577 RGGGATCACTCTCCCAGGTCACGGAGCC (SEQ ID NO: 379) 579 FCTGGGAGAGTGATCCCAACCACNNSTACACGGTTCCTGCGGTG (SEQ ID NO: 380) 579 RGTGGTTGGGATCACTCTCCCAGGTCAC (SEQ ID NO: 381) 583 FTCCCAACCACACTTACACGGTTNNSGCGGTGGCTTGTGTGACG (SEQ ID NO: 382) 583 RAACCGTGTAAGTGTGGTTGGGATCACT (SEQ ID NO: 383)

Example 2 Transformation of TrGA SELs into Trichoderma reesei

The SELs were transformed into T. reesei using the PEG-protoplast method(See e.g., Pentillä et al. (1987) Gene 61:155-164). The E. coli clonesof the SMM's confirmed by sequence analysis were grown overnight at 37°C. in deep well microtiter plates (Greiner Art. No. 780271) containing1.200 μl of 2×YT medium with ampicillin (100 μg/ml) and kanamycin (50μg/ml). Plasmid DNAs were isolated from the cultures using CHEMAGIC®Plasmid Mini Kit (Chemagen—Biopolymer Technologie AG, Baesweiler,Germany) and were transformed individually into a T. reesei host strainderived from RL-P37 bearing four gene deletions (Δcbh1, Δcbh2, Δegl1,Δegl2, i.e., “quad-deleted”; see U.S. Pat. No. 5,847,276, WO 92/06184and WO 05/001036) using the PEG-Protoplast method with the followingmodifications.

For protoplast preparation, spores were grown for 16-24 hours at 24° C.in Trichoderma Minimal Medium (MM) (20 g/L glucose, 15 g/L KH₂PO₄, pH4.5, 5 g/L (NH₄)₂SO₄, 0.6 g/L MgSO₄×7H₂O, 0.6 g/L CaCl₂×2H₂O, 1 ml of1000×T. reesei Trace elements solution {5 g/L FeSO₄×7H₂O, 1.4 g/LZnSO₄×7H₂O, 1.6 g/L MnSO₄×H₂O, 3.7 g/L CoCl₂×6H₂O}) with shaking at 150rpm. Germinating spores were harvested by centrifugation and treatedwith 15 mg/ml of β-D-glucanase-G (Interspex—Art. No. 0439-1) solution tolyse the fungal cell walls. Further preparation of protoplasts wasperformed by a standard method, as described by Penttilä et al. (1987supra). 2) The transformation method was scaled down 10 fold. Ingeneral, transformation mixtures containing up to 600 ng of DNA and1-5×10⁵ protoplasts in a total volume of 25 μl were treated with 200 mlof 25% PEG solution, diluted with 2 volumes of 1.2M sorbitol solution,mixed with 3% selective top agarose MM with acetamide (the same MinimalMedium as mentioned above but (NH₄)₂SO₄ was substituted with 20 mMacetamide) and poured onto 2% selective agarose with acetamide either in24 well microtiter plates or in a 20×20 cm Q-tray divided in 48 wells.The plates were incubated at 28° C. for 5 to 8 days. Spores from thetotal population of transformants regenerated on each individual wellwere harvested from the plates using a solution of 0.85% NaCl, 0.015%Tween 80. Spore suspensions were used to inoculate fermentations in 96wells MTPs. In the case of 24 well MTPs, an additional plating step on afresh 24 well MTP with selective acetamide MM was introduced in order toenrich the spore numbers.

Example 3 Fermentation of T. Reesei Transformants Expressing TrGAVariants in a MTP Format

The transformants were fermented in microtiter filter plates and theculture supernatants containing the expressed protein variants of TrGAobtained were used for assays. In brief, 96 well filter plates (CorningArt. No. 3505) containing 200 μl of LD-GSM medium (5.0 g/L (NH₄)₂SO₄, 33g/L 1,4-piperazinebis(propanesulfonic acid), pH 5.5, 9.0 g/L Casaminoacids, 1.0 g/L KH₂PO₄, 1.0 g/L CaCl₂×2H₂O, 1.0 g/L MgSO₄×7H₂O, 2.5 ml/Lof 1000×T. reesei trace elements, 20 g/L Glucose, 10 g/L Sophorose) wereinoculated in quadruplicate with spore suspensions of T. reeseitransformants expressing TrGA variants (more than 10⁴ spores per well).The plates were incubated at 28° C. with 230 rpm shaking and 80%humidity for 6 days. Culture supernatants were harvested by vacuumfiltration. The supernatants were used in different assays for screeningof variants with improved properties.

Example 4 Preparation of the Whole Broth Samples from GA-ProducingTransformants

TrGA producing transformants were initially pregrown in 250 ml shakeflasks containing 30 ml of Proflo medium. Proflo medium contained: 30g/L α-lactose, 6.5 g/L (NH₄)₂SO₄, 2 g/L KH₂PO₄, 0.3 g/L MgSO₄×7H2O, 0.2g/L CaCl₂×2H₂O, 1 ml/L 1000× trace element salt solution as mentionedabove, 2 ml/L 10% Tween 80, 22.5 g/L ProFlo cottonseed flour (Tradersprotein, Memphis, Tenn.), 0.72 g/L CaCO₃. After two days of growth at28° C. and 140 rpm, 10% of the Proflo culture was transferred into a 250ml shake flask containing 30 ml of Lactose Defined Medium. Thecomposition of the Lactose defined Medium was as follows: 5 g/L(NH₄)₂SO₄, 33 g/L 1,4-piperazinebis(propanesulfonic acid) buffer, pH5.5, 9 g/L casamino acids, 4.5 g/L KH₂PO₄, 1.0 g/L MgSO₄×7H₂O, 5 ml/LMazu DF60-P antifoam (Mazur Chemicals, IL), 1 ml/L of 1000× traceelement solution. 40 ml/L of 40% (w/v) lactose solution was added to themedium after sterilization. Shake flasks with the Lactose Defined mediumwere incubated at 28° C., 140 rpm for 4-5 days.

Mycelium was removed from the culture samples by centrifugation and thesupernatant was analyzed for total protein content (BCA Protein AssayKit, Pierce Cat. No. 23225) and GA activity, as described above in theExperimental section.

The protein profile of the whole broth samples was determined by SDSPAGE electrophoresis. Samples of the culture supernatant were mixed withan equal volume of 2× sample loading buffer with reducing agent andseparated on NUPAGE® Novex 10% Bis-Tris Gel with MES SDS Running Buffer(Invitrogen, Carlsbad, Calif., USA). Polypeptide bands were visualizedin the SDS gel with SIMPLYBLUE SafeStain (Invitrogen, Carlsbad, Calif.,USA).

Example 5-7 provide Variants in the Catalytic domain with improvedproperties. Example 8-10 provide Variants in the starch binding domainwith improved properties.

Example 5 Variants in the Catalytic Domain with Improved ThermalStability

The parent TrGA molecule had a residual activity between 15 and 44%(day-to-day variation) under the conditions described. The performanceindex was calculated based on the WT TrGA thermostability of the samebatch. The performance indices are the quotients PI=(Variant residualactivity)/(WT TrGA residual activity). Using this quotient, aperformance index>1 indicates an improved stability. Variants which hada thermal stability performance index of more than 1.0 are shown in thefollowing Table 2.

TABLE 2 Thermal stability screening Variant PI Thermal Stability T010F1.11 T010G 1.13 T010M 1.12 T010Q 1.06 T010R 1.06 T010S 1.24 T042V 1.31F059A 1.03 F059G 1.07 F059L 1.06 F059M 1.12 F059Q 1.10 F059V 1.03 N061V1.06 E068C 1.23 E068F 1.14 E068G 1.15 E068I 1.19 E068K 1.01 E068M 1.29E068N 1.18 E068Q 1.15 E068W 1.09 A072E 1.07 A072Q 1.02 G073F 1.44 G073M1.01 G073N 1.10 G073W 1.36 S097E 1.08 S097G 1.03 S097T 1.17 S097V 1.03L098C 1.07 A099C 1.07 A099F 1.02 A099I 1.14 A099L 1.09 A099Q 1.07 A099R1.02 A099S 1.11 A099T 1.02 S102A 1.02 K114C 1.19 K114D 1.17 K114E 1.16K114L 1.10 K114M 1.21 K114Q 1.25 I133V 1.21 K140D 1.09 K140Q 1.06 K140S1.05 K140W 1.04 N144A 1.11 N144F 1.06 S152C 1.04 S152G 1.09 S152I 1.09S152N 1.12 N153A 1.28 N153D 1.06 N153E 1.29 N153F 1.16 N153H 1.01 N153L1.06 N153M 1.27 N153S 1.31 N153V 1.34 N153W 1.19 N182R 1.02 A204D 1.02A204M 1.08 T205C 1.02 T205D 1.06 T205N 1.09 T205P 1.17 T205S 1.04 T205V1.06 T205Y 1.07 S214C 1.02 S214E 1.03 S214N 1.07 S214P 1.04 S214Q 1.13S214T 1.06 S214V 1.13 S214W 1.03 S214Y 1.04 V216I 1.13 W228A 1.01 W228F1.12 W228G 1.06 W228H 1.05 W228I 1.06 W228L 1.14 W228M 1.04 W228Q 1.15W228S 1.15 W228T 1.06 W228V 1.21 W228Y 1.10 V229A 1.16 V229D 1.18 V229E1.16 V229F 1.17 V229G 1.18 V229H 1.13 V229I 1.21 V229L 1.20 V229M 1.11V229N 1.07 V229P 1.13 V229Q 1.10 V229R 1.07 V229S 1.12 V229T 1.11 V229W1.07 V229Y 1.08 S230C 1.09 S230D 1.08 S230E 1.11 S230F 1.08 S230G 1.09S230H 1.03 S230K 1.02 S230L 1.02 S230M 1.08 S230N 1.16 S230P 1.12 S230Q1.20 S230R 1.11 S230T 1.07 S230V 1.11 S230Y 1.05 S231A 1.06 S231C 1.07S231D 1.18 S231E 1.10 S231F 1.14 S231K 1.09 S231L 1.15 S231M 1.09 S231N1.13 S231Q 1.18 S231R 1.13 S231T 1.16 S231V 1.21 S231W 1.06 S231Y 1.10D236A 1.10 D236C 1.16 D236E 1.06 D236F 1.11 D236G 1.07 D236H 1.16 D236I1.14 D236K 1.13 D236L 1.08 D236M 1.15 D236N 1.15 D236P 1.06 D236R 1.29D236T 1.16 D236V 1.18 D236Y 1.07 T241V 1.05 N242F 1.03 N242H 1.01 N263A1.18 N263C 1.14 N263L 1.02 N263M 1.10 N263R 1.04 N263T 1.07 L264A 1.03L264D 1.20 L264I 1.14 L264K 1.24 L264M 1.15 L264P 1.02 L264R 1.02 L264V1.04 L264Y 1.15 G265D 1.08 G265E 1.03 G265F 1.08 G265H 1.09 G265I 1.09G265K 1.05 G265L 1.07 G265N 1.15 G265P 1.07 G265Q 1.15 G265R 1.12 G265S1.13 G265T 1.17 G265V 1.15 G265W 1.11 G265Y 1.10 A268C 1.16 A268D 1.20A268E 1.10 A268F 1.07 A268G 1.11 A268I 1.12 A268K 1.11 A268L 1.11 A268M1.18 A268N 1.10 A268P 1.13 A268R 1.15 A268S 1.09 A268T 1.14 A268W 1.05G269K 1.01 G269N 1.08 G269P 1.08 G269Q 1.02 G269R 1.06 D276E 1.03 D276Q1.03 D276S 1.02 D276V 1.17 V284C 1.09 V284E 1.14 V284G 1.13 V284I 1.10V284Q 1.08 V284R 1.09 V284S 1.06 V284T 1.08 V284W 1.08 V284Y 1.12 S291A1.21 S291D 1.02 S291E 1.02 S291F 1.24 S291G 1.05 S291H 1.25 S291I 1.10S291K 1.13 S291M 1.21 S291N 1.08 S291P 1.11 S291Q 1.08 S291R 1.07 S291T1.21 S291V 1.06 S291W 1.15 P300A 1.10 P300N 1.06 P300Q 1.05 P300R 1.02P300T 1.07 P300V 1.02 P300W 1.11 P300Y 1.04 A301A 1.13 A301K 1.11 A301L1.07 A301P 1.22 A301R 1.21 A301S 1.12 A301T 1.14 A301V 1.07 A301W 1.14A301Y 1.14 A303E 1.02 A303I 1.02 A303L 1.03 A303Q 1.01 A311C 1.05 A311E1.06 A311G 1.11 A311H 1.09 A311I 1.04 A311K 1.13 A311L 1.07 A311R 1.07A311S 1.01 A311Y 1.02 V338H 1.12 V338I 1.21 V338L 1.17 V338M 1.13 V338N1.23 V338P 1.18 V338Q 1.20 V338S 1.19 V338Y 1.10 T342C 1.06 T342I 1.04T342L 1.17 T342P 1.08 S344A 1.05 S344C 1.16 S344D 1.02 S344F 1.10 S344K1.12 S344M 1.26 S344N 1.16 S344P 1.20 S344Q 1.22 S344R 1.22 S344T 1.19S344V 1.20 S344W 1.03 T346D 1.03 T346L 1.02 T346M 1.07 T346N 1.15 T346P1.13 T346Q 1.12 T346S 1.13 T346V 1.09 T346W 1.06 T346Y 1.07 A349D 1.15A349E 1.13 A349F 1.09 A349G 1.12 A349H 1.11 A349K 1.14 A349L 1.16 A349M1.07 A349N 1.09 A349P 1.03 A349Q 1.09 A349R 1.04 A349T 1.09 A349V 1.08A349W 1.04 A349Y 1.04 V359Q 1.02 V359R 1.13 V359Y 1.01 G361A 1.13 G361C1.16 G361D 1.35 G361E 1.24 G361F 1.20 G361H 1.11 G361I 1.20 G361K 1.16G361L 1.22 G361M 1.28 G361P 1.27 G361R 1.19 G361S 1.22 G361T 1.16 G361V1.15 G361W 1.22 G361Y 1.26 A364C 1.18 A364D 1.25 A364E 1.27 A364F 1.33A364G 1.25 A364K 1.27 A364L 1.31 A364M 1.21 A364Q 1.19 A364R 1.28 A364S1.23 A364T 1.23 A364V 1.23 A364W 1.23 T375A 1.17 T375E 1.03 T375F 1.06T375G 1.05 T375H 1.13 T375K 1.10 T375L 1.03 T375M 1.17 T375N 1.20 T375P1.15 T375V 1.16 T375W 1.11 T375Y 1.17 N379A 1.11 N379C 1.03 N379D 1.06N379F 1.07 N379G 1.09 N379H 1.07 N379I 1.04 N379K 1.04 N379L 1.04 N379M1.08 N379P 1.17 N379Q 1.11 N379R 1.07 N379T 1.09 N379V 1.13 N379W 1.09N379Y 1.06 S382A 1.06 S382D 1.04 S382E 1.05 S382G 1.06 S382I 1.07 S382K1.03 S382N 1.07 S382P 1.10 S382R 1.05 S382T 1.02 S382Y 1.04 S390M 1.06S390Q 1.02 S390R 1.02 E391L 1.04 E391R 1.02 E391S 1.02 E391W 1.04 E391Y1.02 A393D 1.11 A393E 1.03 A393F 1.09 A393G 1.12 A393H 1.05 A393I 1.06A393K 1.05 A393L 1.17 A393M 1.07 A393N 1.11 A393Q 1.02 A393R 1.03 A393S1.13 A393T 1.08 A393V 1.09 A393W 1.10 A393Y 1.12 K394A 1.08 K394C 1.06K394E 1.07 K394F 1.09 K394G 1.05 K394H 1.08 K394L 1.08 K394M 1.06 K394Q1.07 K394R 1.06 K394T 1.03 K394V 1.02 S410E 1.05 S410H 1.11 S410I 1.06S410K 1.11 S410L 1.05 S410M 1.02 S410N 1.10 S410Q 1.15 S410R 1.18 S410T1.04 S410V 1.13 L417I 1.04 L417K 1.20 L417M 1.05 L417Q 1.04 L417R 1.20L417V 1.07 L417Y 1.01 T430A 1.05 T430E 1.02 T430F 1.06 T430H 1.10 T430I1.04 T430K 1.08 T430M 1.17 T430N 1.13 T430Q 1.05 T430R 1.13 T430S 1.17T430V 1.05 A431I 1.03 A431N 1.03 A431P 1.08 A431R 1.08 A431V 1.03 R433A1.13 R433C 1.24 R433E 1.22 R433F 1.17 R433G 1.23 R433K 1.12 R433L 1.23R433M 1.10 R433N 1.28 R433S 1.23 R433V 1.28 R433W 1.16 R433Y 1.18 I436E1.07 I436F 1.02 I436G 1.09 I436H 1.20 I436K 1.14 I436P 1.15 I436R 1.16I436S 1.17 I436T 1.18 I436V 1.12 I436Y 1.05 A442N 1.06 A442R 1.04 A442T1.09 S444E 1.04 S444K 1.07 S444M 1.05 S444Q 1.04 T448A 1.02 T448E 1.09T448F 1.12 T448I 1.12 T448L 1.09 T448M 1.11 T448Q 1.17 T448R 1.09 T448S1.07 T448V 1.13 T448W 1.01 T448Y 1.08 S451E 1.04 S451H 1.18 S451K 1.08S451L 1.01 S451Q 1.06 S451T 1.02

Example 6 Variants in the Catalytic Domain with Improved SpecificActivity (SA) in an Ethanol Screening Assay

Variants were tested in an ethanol screening assay using the assaysdescribed above. Table 3 shows the results of the screening assay forvariants with a Performance Index (PI)>1.0 compared to the parent TrGAPI. The PI of the specific activity is the quotient “Variant-specificactivity/WT-specific activity.” Using this, the PI of the specificactivity for the wild type TrGA is 1.0 and a variant with a PI>1.0 has aspecific activity greater than the parent TrGA. The specific activitywas determined in this example as the activity measured by the ethanolscreening assay divided by the results obtained in the Caliper assaydescribed above.

TABLE 3 Ethanol Screening Variant PI Specific Activity T010D 1.09 T010F1.06 T010G 1.12 T010K 1.05 T010L 1.07 T010M 1.05 T010P 1.05 T010R 1.08T010S 1.09 L014E 1.03 L014H 1.05 N015D 1.02 P023A 1.16 P023F 1.13 P023N1.05 F059A 1.17 F059F 1.05 F059G 1.05 K060F 1.06 K060H 1.03 N061D 1.05N061I 1.21 N061L 1.18 N061Q 1.08 N061V 1.11 N061W 1.02 R065A 1.17 R065C1.08 R065G 1.08 R065I 1.11 R065K 1.09 R065M 1.07 R065S 1.12 R065V 1.14R065Y 1.01 T067C 1.14 T067I 1.13 T067K 1.05 T067M 1.22 E068I 1.06 E068M1.10 E068W 1.03 A072E 1.11 A072G 1.02 A072L 1.03 A072M 1.11 A072Q 1.10A072R 1.10 A072W 1.06 A072Y 1.30 G073C 1.02 G073L 1.07 G073W 1.03 S097F1.11 S097M 1.11 S097N 1.23 S097P 1.18 S097R 1.07 S097V 1.12 S097W 1.09S097Y 1.18 L098H 1.04 L098M 1.09 A099C 1.07 A099L 1.01 A099M 1.03 A099N1.11 A099P 1.08 S102A 1.20 S102C 1.04 S102I 1.04 S102L 1.05 S102M 1.25S102N 1.19 S102R 1.21 S102V 1.07 S102W 1.06 S102Y 1.10 E110Q 1.02 E110S1.07 E110W 1.11 L113E 1.15 L113N 1.08 I133K 1.04 I133R 1.16 I133S 1.08I133T 1.29 K140A 1.04 K140E 1.04 K140F 1.03 K140H 1.14 K140L 1.10 K140M1.11 K140N 1.15 K140Q 1.08 K140R 1.12 K140S 1.13 K140V 1.15 K140W 1.07K140Y 1.06 N144C 1.05 N144D 1.15 N144E 1.16 N144I 1.13 N144K 1.05 N145A1.07 N145C 1.09 N145E 1.03 N145I 1.20 N145K 1.05 N145L 1.03 N145M 1.07N145Q 1.14 N145R 1.11 N145V 1.12 N145W 1.14 N145Y 1.05 Y147A 1.02 Y147M1.02 Y147R 1.12 S152H 1.08 S152M 1.10 N153C 1.09 N153D 1.20 N153K 1.13N153L 1.12 N153W 1.07 N153Y 1.13 N164A 1.02 N164G 1.03 N182C 1.12 N182E1.13 N182K 1.07 N182P 1.01 N182R 1.03 A204C 1.04 A204D 1.09 A204G 1.02A204I 1.06 A204M 1.09 A204Q 1.09 A204T 1.05 T205A 1.03 T205D 1.03 T205H1.03 T205I 1.05 T205K 1.09 T205M 1.05 T205N 1.09 T205P 1.17 T205Q 1.25T205S 1.10 T205V 1.06 T205W 1.05 T205Y 1.18 S214P 1.08 S214T 1.07 V216C1.08 V216G 1.05 V216H 1.03 V216K 1.02 V216N 1.13 V216Y 1.09 Q219D 1.05Q219G 1.06 Q219H 1.03 Q219N 1.08 Q219P 1.16 Q219S 1.29 W228A 1.20 W228F1.22 W228G 1.17 W228H 1.33 W228I 1.18 W228L 1.12 W228M 1.35 W228T 1.19V229E 1.01 V229I 1.02 V229M 1.03 V229N 1.01 V229Q 1.02 S230C 1.23 S230D1.13 S230E 1.10 S230F 1.63 S230G 1.77 S230H 1.05 S230I 1.18 S230K 1.04S230L 1.20 S230N 1.23 S230P 1.13 S230Q 1.20 S230R 1.84 S230T 1.11 S230V1.12 S230Y 1.08 S231C 1.13 S231D 1.08 S231F 1.17 S231L 1.29 S231M 1.08S231N 1.04 S231Q 1.05 S231R 1.02 S231V 1.07 S231Y 1.07 D236F 1.14 D236G1.05 D236L 1.11 D236M 1.07 D236N 1.03 D236P 1.06 D236S 1.03 D236T 1.14D236V 1.04 I239M 1.04 I239Q 1.08 I239S 1.11 I239V 1.52 I239W 1.02 I239Y1.25 T241C 1.07 T241E 1.03 T241H 1.10 T241L 1.04 T241M 1.05 T241P 1.02T241S 1.08 T24IV 1.05 N242C 1.08 N242F 1.06 N242M 1.04 N242T 1.08 N242V1.03 N242W 1.05 N263H 1.05 N263K 1.02 N263P 1.40 L264A 1.04 L264C 1.08L264E 1.16 L264F 1.03 L264S 1.05 G265E 1.10 G265H 1.12 G265I 1.06 G265K1.03 G265R 1.06 G265T 1.10 A268C 1.50 A268D 1.14 A268E 1.18 A268F 1.15A268G 1.35 A268I 1.15 A268K 1.23 A268L 1.06 A268P 1.08 A268R 1.14 A268T1.18 A268W 1.05 G269E 1.01 D276S 1.01 V284R 1.06 V284T 1.05 V284Y 1.07S291A 1.26 S291E 1.09 S291F 1.13 S291H 1.13 S291K 1.07 S291N 1.04 S291P1.12 S291W 1.04 P300K 1.10 P300P 1.12 P300R 1.11 A301A 1.01 A301E 1.09A301K 1.09 A301L 1.05 A301P 1.02 A301S 1.03 A301W 1.04 A303C 1.06 A303D1.04 A303F 1.09 A303H 1.05 A303I 1.09 A303K 1.02 A303L 1.05 A303N 1.04A303R 1.10 A303T 1.11 A303V 1.04 A303W 1.15 A303Y 1.07 A311N 1.04 A311P1.09 A311Q 1.19 A311S 1.01 A311Y 1.06 V338P 1.04 V338Q 1.12 V338S 1.14V338Y 1.05 T342N 1.06 T342V 1.23 S344A 1.05 S344T 1.01 T346G 1.14 T346H1.07 T346M 1.06 T346N 1.09 T346P 1.07 T346Q 1.04 T346Y 1.06 A349L 1.02V359I 1.14 V359K 1.08 V359M 1.09 V359N 1.02 V359Q 1.14 V359R 1.15 V359W1.04 G361H 1.11 G361L 1.04 G361R 1.04 A364M 1.05 A364W 1.07 T375C 1.12T375D 1.01 T375E 1.02 T375H 1.05 T375V 1.04 T375W 1.02 T375Y 1.05 N379A1.05 N379C 1.10 N379D 1.05 N379G 1.07 N379F 1.01 N379M 1.04 N379P 1.06N379S 1.01 S382A 1.02 S382N 1.02 S382P 1.10 S382S 1.09 S382V 1.10 S382W1.10 S390A 1.05 S390Y 1.03 E391A 1.17 E391E 1.10 E391I 1.13 E391K 1.18E391L 1.18 E391M 1.05 E391Q 1.04 E391R 1.08 E391V 1.05 E391W 1.12 E391Y1.08 A393E 1.05 A393G 1.14 A393H 1.10 A393I 1.07 A393K 1.09 A393L 1.12A393M 1.07 A393N 1.18 A393Q 1.02 A393R 1.09 A393S 1.10 A393T 1.13 A393V1.16 A393W 1.04 A393Y 1.03 K394A 1.11 K394H 1.11 K394K 1.08 K394L 1.01K394M 1.14 K394Q 1.09 K394R 1.19 K394S 1.22 K394T 1.08 K394V 1.05 K394W1.13 S410E 1.01 S410H 1.06 S410N 1.04 L417A 1.12 L417D 1.19 L417E 1.10L417F 1.08 L417G 1.19 L417I 1.10 L417K 1.02 L417Q 1.04 L417R 1.30 L417S1.05 L417T 1.10 L417V 1.21 L417W 1.05 L417Y 1.10 H418E 1.01 H418M 1.12T430A 1.19 T430E 1.15 T430F 1.09 T430G 1.16 T430H 1.15 T430I 1.06 T430K1.24 T430M 1.16 T430N 1.07 T430Q 1.15 T430R 1.04 T430V 1.09 A431C 1.04A431E 1.08 A431H 1.11 A431I 1.20 A431L 1.21 A431M 1.12 A431Q 1.22 A431R1.11 A431S 1.09 A431W 1.04 A431Y 1.13 R433A 1.09 R433M 1.17 R433W 1.06R433Y 1.22 A442A 1.13 S444K 1.03 S444M 1.13 S444N 1.04 S444P 1.08 S444Q1.08 S444R 1.03 S444T 1.15 S444V 1.14 S444W 1.16 T448F 1.02 T448G 1.08T448I 1.10 T448P 1.08 T448Q 1.04 T448V 1.04 T451K 1.29

Example 7 Combined Specific Activity and Thermostability Variants in theCatalytic Domain

Table 4 shows the variants that had a performance index (PI) of 1.0 orbetter as compared to the parent for both properties: specific activityand thermostability. These included the following sites: 10, 15, 59, 61,68, 72, 73, 97, 99, 102, 133, 140, 153, 182, 204, 205, 214, 228, 229,230, 231, 236, 241, 242, 264, 265, 268, 275, 284, 291, 300, 301, 303,311, 338, 344, 346, 359, 361, 364, 375, 370, 382, 391, 393, 394, 410,417, 430, 431, 433, 444, 448, and 451. The sites showing the highestspecific activity and thermostability combined included: 228, 230, 231,268, 291, 417, 433, and 451.

TABLE 4 Combined variants PI of Specific PI of Thermal Variant ActivityStability T010F 1.06 1.11 T010G 1.12 1.13 T010M 1.05 1.12 T010R 1.081.06 T010S 1.09 1.24 N015N 1.06 1.06 F059A 1.17 1.03 F059G 1.05 1.07N061V 1.11 1.06 E068I 1.06 1.19 E068M 1.10 1.29 E068W 1.03 1.09 A072E1.11 1.07 A072Q 1.10 1.02 G073W 1.03 1.36 S097V 1.12 1.03 A099C 1.071.07 A099L 1.01 1.09 S102A 1.20 1.02 K140Q 1.08 1.06 K140S 1.13 1.05K140W 1.07 1.04 N153D 1.20 1.06 N153L 1.12 1.06 N153W 1.07 1.19 N182R1.03 1.02 A204D 1.09 1.02 A204M 1.09 1.08 T205D 1.03 1.06 T205N 1.091.09 T205P 1.17 1.17 T205S 1.10 1.04 T205V 1.06 1.06 T205Y 1.18 1.07S214P 1.08 1.04 S214T 1.07 1.06 W228A 1.20 1.01 W228F 1.22 1.12 W228G1.17 1.06 W228H 1.33 1.05 W228I 1.18 1.06 W228L 1.12 1.14 W228M 1.351.04 W228T 1.19 1.06 V229E 1.01 1.16 V229I 1.02 1.21 V229M 1.03 1.11V229N 1.01 1.07 V229Q 1.02 1.10 S230C 1.23 1.09 S230D 1.13 1.08 S230E1.10 1.11 S230F 1.63 1.08 S230G 1.77 1.09 S230H 1.05 1.03 S230K 1.041.02 S230L 1.20 1.02 S230N 1.23 1.16 S230P 1.13 1.12 S230Q 1.20 1.20S230R 1.84 1.11 S230T 1.11 1.07 S230V 1.12 1.11 S230Y 1.08 1.05 S231C1.13 1.07 S231D 1.08 1.18 S231F 1.17 1.14 S231L 1.29 1.15 S231M 1.081.09 S231N 1.04 1.13 S231Q 1.05 1.18 S231R 1.02 1.13 S231V 1.07 1.21S231Y 1.07 1.10 D236F 1.14 1.11 D236G 1.05 1.07 D236L 1.11 1.08 D236M1.07 1.15 D236N 1.03 1.15 D236P 1.06 1.06 D236T 1.14 1.16 D236V 1.041.18 T241V 1.05 1.05 N242F 1.06 1.03 L264A 1.04 1.03 G265E 1.10 1.03G265H 1.12 1.09 G265I 1.06 1.09 G265K 1.03 1.05 G265R 1.06 1.12 G265T1.10 1.17 A268C 1.50 1.16 A268D 1.14 1.20 A268E 1.18 1.10 A268F 1.151.07 A268G 1.35 1.11 A268I 1.15 1.12 A268K 1.23 1.11 A268L 1.06 1.11A268P 1.08 1.13 A268R 1.14 1.15 A268T 1.18 1.14 A268W 1.05 1.05 D276S1.01 1.02 V284R 1.06 1.09 V284T 1.05 1.08 V284Y 1.07 1.12 S291A 1.261.21 S291E 1.09 1.02 S291F 1.13 1.24 S291H 1.13 1.25 S291K 1.07 1.13S291N 1.04 1.08 S291P 1.12 1.11 S291W 1.04 1.15 P300R 1.11 1.02 A301K1.09 1.11 A301L 1.05 1.07 A301P 1.02 1.22 A301S 1.03 1.12 A301W 1.041.14 A303I 1.09 1.02 A303L 1.05 1.03 A311S 1.01 1.01 A311Y 1.06 1.02V338P 1.04 1.18 V338Q 1.12 1.20 V338S 1.14 1.19 V338Y 1.05 1.10 S344A1.05 1.05 S344T 1.01 1.19 T346M 1.06 1.07 T346N 1.09 1.15 T346P 1.071.13 T346Q 1.04 1.12 T346Y 1.06 1.07 A349L 1.02 1.16 V359Q 1.14 1.02V359R 1.15 1.13 G361H 1.11 1.11 G361L 1.04 1.22 G361R 1.04 1.19 A364M1.05 1.21 A364W 1.07 1.23 T375E 1.02 1.03 T375H 1.05 1.13 T375V 1.041.16 T375W 1.02 1.11 T375Y 1.05 1.17 N379A 1.05 1.11 N379C 1.10 1.03N379D 1.05 1.06 N379G 1.07 1.09 N379I 1.01 1.04 N379M 1.04 1.08 N379P1.06 1.17 S382A 1.02 1.06 S382N 1.02 1.07 S382P 1.10 1.10 E391L 1.181.04 E391R 1.08 1.02 E391W 1.12 1.04 E391Y 1.08 1.02 A393E 1.05 1.03A393G 1.14 1.12 A393H 1.10 1.05 A393I 1.07 1.06 A393K 1.09 1.05 A393L1.12 1.17 A393M 1.07 1.07 A393N 1.18 1.11 A393Q 1.02 1.02 A393R 1.091.03 A393S 1.10 1.13 A393T 1.13 1.08 A393V 1.16 1.09 A393W 1.04 1.10A393Y 1.03 1.12 K394A 1.11 1.08 K394H 1.11 1.08 K394L 1.01 1.08 K394M1.14 1.06 K394Q 1.09 1.07 K394R 1.19 1.06 K394T 1.08 1.03 K394V 1.051.02 S410E 1.01 1.05 S410H 1.06 1.11 S410N 1.04 1.10 L417I 1.10 1.04L417K 1.02 1.20 L417Q 1.04 1.04 L417R 1.30 1.20 L417V 1.21 1.07 L417Y1.10 1.01 T430A 1.19 1.05 T430E 1.15 1.02 T430F 1.09 1.06 T430H 1.151.10 T430I 1.06 1.04 T430K 1.24 1.08 T430M 1.16 1.17 T430N 1.07 1.13T430Q 1.15 1.05 T430R 1.04 1.13 T430V 1.09 1.05 A431I 1.20 1.03 A431R1.11 1.08 R433A 1.09 1.13 R433M 1.17 1.10 R433W 1.06 1.16 R433Y 1.221.18 S444K 1.03 1.07 S444M 1.13 1.05 S444Q 1.08 1.04 T448F 1.02 1.12T448I 1.10 1.12 T448Q 1.04 1.17 T448V 1.04 1.13 S451K 1.29 1.08

Example 8 Starch Binding Domain Variants with Improved Thermal Stability

The parent TrGA molecule had a residual activity between 15 and 44%(day-to-day variation) under the conditions described. The performanceindex was calculated based on the WT TrGA thermostability of the samebatch. The performance indices are the quotients PI=(Variant residualactivity)/(TrGA WT residual activity). Using this quotient, aperformance index>1 indicates an improved stability. Variants which hada thermal stability performance index of more than 1.0 are shown in thefollowing Table 5.

TABLE 5 SBD -Thermal stability screening Variant PI of thermal stabilityT493I 1.15 T495K 1.20 T495R 1.10 T495S 1.23 E503A 1.43 E503C 1.39 E503S1.02 E503T 1.04 E503V 1.68 Q508H 1.19 Q508R 1.29 Q508S 1.13 Q511A 1.11Q511D 1.12 Q511H 1.33 Q511N 1.14 Q511S 1.15 N518S 1.17 A519E 1.11 A519K1.33 A519R 1.32 A519T 1.06 A519V 1.07 A519Y 1.29 A520C 1.10 A520L 1.06A520P 1.06 T527A 1.08 T527V 1.12 V531L 1.21 A535D 1.12 A535K 1.24 A535N1.37 A535P 1.59 A535R 1.26 V536I 1.02 V536R 1.10 N537W 1.16 A539E 1.32A539H 1.17 A539M 1.05 A539R 1.36 A539S 1.30 N563A 1.14 N563C 1.49 N563E1.44 N563I 1.65 N563K 1.77 N563L 1.60 N563Q 1.29 N563T 1.31 N563V 1.53N577A 1.19 N577K 1.23 N577P 1.41 N577R 1.31 N577V 1.12

Example 9 Starch Binding Domain Variants with Improved Specific Activity(SA) in an Ethanol Screening Assay

Variants were tested in an ethanol screening assay using the assaysdescribed above. Table 6 shows the results of the screening assay forvariants with a Performance Index (PI)>1.0 compared to the parent TrGAPI. The PI of the mutations showed a performance index of the specificactivity for the wild type TrGA is 1.0 and a variant with a wide varietyof substitutions at these sites resulted in increased thermostability.These sites included 539.

TABLE 6 SBD Ethanol Screening Variant PI Specific Activity T493C 1.05T493M 1.19 T493N 1.07 T493Q 1.03 T493Y 1.07 P494H 1.03 P494I 1.12 P494M1.12 P494N 1.16 P494Q 1.02 P494W 1.07 T495M 1.49 T495P 1.04 T495R 1.15H502A 1.16 H502M 1.13 H502S 1.15 H502V 1.10 E503C 1.05 E503D 1.06 E503H1.01 E503S 1.10 E503W 1.04 Q508N 1.11 Q508P 1.07 Q508Y 1.09 Q511C 1.07Q511G 1.06 Q511H 1.05 Q511I 1.10 Q511K 1.09 Q511T 1.04 Q511V 1.04 N518P1.13 N518T 1.02 A519I 1.21 A520C 1.38 A520E 1.16 A520L 1.46 A520P 1.50A520Q 1.05 A520R 1.06 A520W 1.07 V531A 1.02 V531L 1.04 V531N 1.19 V531R1.06 V531S 1.08 V531T 1.19 A535E 1.19 A535F 1.06 A535G 1.02 A535K 1.07A535L 1.02 A535N 1.04 A535P 1.14 A535R 1.22 A535S 1.06 A535T 1.04 A535V1.04 A535W 1.09 A535Y 1.13 V536C 1.09 V536E 1.09 V536I 1.04 V536L 1.07V536M 1.20 V536Q 1.02 V536S 1.05 A539E 1.08 A539M 1.03 A539S 1.02 A539W1.06 A539R 1.22

Example 10 Glucoamylase Variants Having Increased SA and Thermostability

The variants in examples 8 and 9 were analyzed for combined increasedspecific activity and increased thermal stability. Table 7 shows thevariants with a Performance Index (PI)>1.0 compared to the parent TrGAPI for both properties.

TABLE 7 SBD variants with combined altered properties PI Specific PIThermal Variant Activity Stability T495R 1.15 1.10 E503C 1.05 1.39 E503S1.10 1.02 Q511H 1.05 1.33 A520C 1.38 1.10 A520L 1.46 1.06 A520P 1.501.06 V531L 1.04 1.21 A535K 1.07 1.24 A535N 1.04 1.37 A535P 1.14 1.59A535R 1.22 1.26 V536I 1.04 1.02 A539E 1.08 1.32 A539M 1.03 1.05 A539R1.22 1.36 A539S 1.02 1.30

Example 11 Crystal Structure of TrGA

The complete three dimensional structure of Trichoderma reesei (Hypocreajecorina) glucoamylase (TrGA) was determined at 1.9 Å resolution. Table8 shows the coordinates for the Trichoderma glucoamylase crystalstructure. TrGA was crystallized in an intact form containing 599residues and all post-translational modifications that would normallyoccur in the natural host. The crystal structure was produced andanalyzed as follows:

Protein expression and purification—The gene encoding H. jecorina GA wascloned and expressed according to the protocols described in the USpatent application publication No.: US 2006/0094080 A1, Dunn-Coleman etal. May 4, 2006.

The TrGA protein material used for all crystallization experiments wasinitially purified in one step by anion exchange chromatography asfollows: concentrated culture supernatants of expressed TrGA, consistingof 180 mg/ml total protein, were prepared by diluting sample 1:10 in a25 mM Tris-HCl, pH 8.0 buffer. A HIPREP 16/10 Q Sepharose FF column (GEHealthcare) was employed for the anion exchange purification. The HIPREPcolumn was equilibrated with 4 column volumes (CV) starting buffer (25mM Tris-HCl, pH 8.0) followed by application of 10 ml of the dilutedprotein sample. An 8 CV linear gradient of 0 to 140 mM NaCl in therunning buffer (25 mM Tris-HCl, pH 8.0) was applied to elute boundprotein. Bound TrGA eluted from the HIPREP Q sepharose column at a saltconcentration of approximately 80 mM NaCl. Fractions containing pureTrGA protein were pooled and concentrated to 50 mg/ml using a 25 mlVIVASPIN centrifugal concentration tube (Viva Science) with a molecularweight cutoff (MWCO) of 10 kD. Purified and concentrated TrGA materialwas buffer exchanged using a DG-10 desalting column (Bio-Rad)equilibrated with 50 mM sodium acetate buffer, pH 4.3. Proteinconcentrations were determined by measuring the absorbance at 280 nm.The initially purified and concentrated TrGA protein stock was stored at−20° C.

Two additional purification steps, an additional anion exchangepurification, and a size exclusion purification, were introduced toenhance the TrGA protein material's propensity to form crystals. Thesetwo additional purification steps were performed as follows: In thefirst anion exchange purification step a 10 ml MONOQ column (GEHealthcare) was employed. A Sample of 1 ml of the initially purified andfrozen TrGA material (50 mg protein) was thawed and the buffer waschanged to 20 mM Tris-HCl, pH 8.0, by repeated dilution of the sample to6 ml in the new buffer, followed by a concentration of the sample againto 0.5 ml using a 6 ml 5 kD MWCO concentration tube. The TrGA sample wasdiluted after the last concentration step in distilled water until aconductivity of the protein sample was reached that corresponded to theconductivity of the starting buffer of the anion purification, i.e. 25mM Tris-HCl, pH 8.0. The MONOQ column was first equilibrated with 4column volumes (CV) starting buffer, followed by application of thediluted protein sample to the column. Bound protein was eluted from theMONOQ column by two different gradients. In the first a 4 CV linear pHgradient was applied where the pH of the starting buffer was decreasedfrom 8.0 to 6.0. In the second gradient an 8 CV long salt gradient wasapplied in which the salt concentration was increased from 0 to 350 mMNaCl in the running buffer (25 mM Tris-HCl, pH 6.0). Bound TrGA wasfound to elute from the column during the second salt gradient at anapproximate NaCl concentration of 150 mM. Fractions containing TrGA werepooled and concentrated to 2 ml using a 6 ml 5 kD MWCO VIVASPINconcentration tube. The concentrated TrGA sample was thereafter appliedto a Superdex 200 16/60 size exclusion column (GE Healthcare)equilibrated with 4 CV of 20 mM Tris-Cl, pH 8.0, and 50 mM NaCl, whichalso was used as running buffer. Fractions from the main elution peakafter the size exclusion purification were pooled and concentrated to anapproximate protein concentration of 7.5 mg/ml using a 6 ml 5 kD MWCOVIVASPIN concentration tube.

Protein crystallization—The protein sample that was used to find theinitial TrGA crystallization conditions was a sample of the TrGAmaterial that was purified once by anion exchange purification andthereafter stored at −20° C. The TrGA protein sample was thawed anddiluted with 50 mM sodium acetate buffer, pH 4.3, to approximately 12mg/ml, prior to the initial crystallization experiments. Theorthorhombic x-ray dataset, was used to solve the TrGA structure bymolecular replacement (MR), and the high-resolution orthorhombic datasetused for the final orthorhombic space group TrGA structure model. Theorthorhombic TrGA crystals were found to grow in solution consisting of25% PEG 3350, 0.20M ammonium acetate, 0.10M Bis-Tris pH 5.5 (reservoirsolution), using the vapor-diffusion method with hanging drops(McPherson 1982), at 20° C. Crystallization drops were prepared bymixing equal amounts of protein solution (12 mg/ml) and reservoirsolution to a final volume of 10 μl. The TrGA crystals were found tobelong to the orthorhombic space group P212121 with approximate celldimensions: a=52.2 Å, b=99.2 Å, c=121.2 Å, and have a calculated V_(m)of 2.3 (Matthews 1968) with one molecule in the asymmetric unit.

X-ray data collection—The two orthorhombic TrGA datasets were collectedfrom single crystals mounted in sealed capillary tubes, at roomtemperature. The initial lo-resolution orthorhombic TrGA x-ray dataset,used to solve the structure by molecular replacement methods (MR), wascollected on a home x-ray source, an MSC/Rigaku (Molecular StructuresCorp., The Woodlands, Tex.) Raxis IV++ image plate detector withfocusing mirrors using Cu Kα radiation from a Rigaku RU200 rotatinganode generator. This dataset was processed, scaled, and averaged usingthe d*trek software provided by MSC/Rigaku. The C centered monoclinicdataset was collected from a single frozen TrGA crystal at 100K,equilibrated in a cryo-protective agent comprised of 25% PEG 3350, 15%Glycerol 50 mM CaCl₂ and 0.1 M Bis-Tris pH 5.5 as cryoprotectant,mounted in rayon-fiber loops, and plunge frozen in liquid nitrogen priorto transportation to the synchrotron. The high-resolution orthorhombic(1.9 Å) data set and the C centric monoclinic dataset (1.8 Å) were bothcollected at a synchrotron source, beam line 911:5 at MAX LAB in Lund,Sweden. Both datasets that were collected at a synchrotron source wereprocessed with MOSFLM, and scaled with program SCALA included in theCCP4 program package (Collaborative Computational Project Number 41994). All subsequent data processing was performed using the CCP4program package (Collaborative Computational Project Number 4 1994),unless otherwise stated. A set of 5% of the reflections from each dataset was set aside and used for monitoring the R-free (Bruger et al.(1992) 355: 472-475).

Structure solution—The TrGA structure was initially solved by MR withthe automatic replacement program MOLREP (Collaborative ComputationalProject Number 4 1994), included in the CCP4 program package, using theinitial lo-resolution orthorhombic dataset, and using the coordinates ofAspergillus awamori GA (AaGA) variant X100 (pdb entry IGLM (Aleshin etal. (1994) J Mol Biol 238: 575-591) as search model. The A. awamori GAsearch model was edited to remove all glycosylation moieties attached tothe protein molecule as N- and O-glycosylations, and all solventmolecules before carrying out the MR experiments. All reflectionsbetween 36.8 and 2.8 Å resolution, from the initial low resolution TrGAdataset was used for the MR solution. The MR program found a singlerotation function solution, with a maxima of 11.1σ above background, thenext highest maxima was 3.8σ above the background. The translationfunction solution gave an R-factor of 48.7% and had a contrast factor of17.4. The MR solution was refined for 10 cycles of restrained leastsquares refinement using the program Refmac 5.0 (Murshudov et al. (1997)Acta Crystallogr., D53: 240-255). This lowered the crystallographicR-factor to 31.1% while the R-free value dropped from 42.2% to 41.1%.

Model fitting and refinement—The refined MR solution model was used tocalculate an initial density map from the lo-resolution orthorhombicTrGA dataset. Electron density for a disulfide bridge between residues19 and 26 of TrGA, a disulfide bridge not present in the A. awamorivariant X100 structure model, could readily be identified in thiselectron density map. This was taken as an indication that the electrondensity map was of sufficient quality to be used to build a structuremodel of TrGA from its amino acid sequence. The initial TrGA structuremodel, based on the lo-resolution dataset, was refined with alternatingcycles of model building using Coot (Emsley, et al. Acta Crystallogr DBiol Crystallogr (2004) 60:2126-2132), and maximum likelihood refinementusing Refmac 5.0.

The resolution of the initial TrGA structure model was extended to theresolution of the high-resolution orthorhombic dataset (1.9 Å) byrefining the initial TrGA structure model against the high-resolutiondataset for 10 cycles of restrained refinement using the program Refmac5.0. Most water molecules in the structure models were locatedautomatically by using the water picking protocols in the refinementprograms, and then manually selected or discarded by inspection by eye.All structural comparisons were made with either Coot (Emsley et al,supra) or O (Jones et al. (1991) Acta Crystallogr. A47: 110-119), andfigures were prepared with PyMOL (DeLano et al. (2002) The PyMOLMolecular Graphics system. Palo Alto, Calif. USA: DeLano Scientific).

From these results, it can be seen that the TrGA catalytic core segmentfollowed the same (α/α)₆-barrel topology described by Aleshin et al.(supra) for the AaGA, consisting of a double barrel of alpha heliceswith the C-terminal of the outer helix leading into the N-terminus of aninner helix. It was possible to identify key differences in the electrondensity such as the disulfide bridge between residues 19 and 26 and atinsertion (residues 257-260) relative to AaGA. The segment comprising80-100 also underwent extensive model rebuilding. One majorglycosylation site was identified at Asn 171, which had up to fourglycoside moieties attached. A similar glycosylation site was identifiedin AaGA. Additionally, the catalytic core containing three cis-peptidesbetween residues 22-23, 44-45 and 122-123 were conserved between TrGAand AaGA. Overall there was an rms variation of 0.535 Å between 409 outof 453 Cα atoms when comparing the coordinates of the catalytic cores ofTrGA and AaGA.

Example 12 Homology Between TrGA and Aspergillus awamori GA

The crystal structure of the TrGA identified in Example 11, wassuperposed on the previously identified crystal structure of theAspergillus awamori GA (AaGA). The AaGA crystal structure was obtainedfrom the protein database (PDB) and the form of AaGa that wascrystallized was the form containing only a catalytic domain. Thestructure of the Trichoderma reesei glucoamylase with all three regionsintact was determined to 1.8 Angstrom resolution herein (see Table 8 andExample 11). Using the coordinates (see Table 8) the structure wasaligned with the coordinates of the catalytic domain from Aspergillusawamori strain X100 that was determined previously (Aleshin, (1994) JMol Biol 238: 575-591 and the PDB). As seen in FIGS. 6 and 7 thestructure of the catalytic domain overlapped very closely and allowedthe identification of equivalent residues based on this structuralsuperposition.

TrGA Catalytic Domain

Based on this analysis, sites were identified that could be mutated inthe TrGA catalytic domain and result in increased stability and/orspecific activity. These sites include 108, 124, 175 and 316 at theactive site. Also identified were specific pairwise variants Y47W/Y315Fand Y47F/Y315W. Other sites identified were 143, D44, P45, D46, R122,R125, V181, E242, Y310, D313, V314, N317, R408, and N409. Because of thehigh structural homology it is expected that beneficial variants foundat sites in Trichoderma reesei GA would have similar consequences inAspergillus awamori and other homologous glucoamylases.

TrGA Starch Binding Domain and Linker Region

The TrGA linker, residues 454-490 is defined as the segment spanning theregion between two disulfide bridges, one between residues 222 and 453and one between residues 491 and 587. Nine of the residues in the linkerare proline. From the crystal structure, the linker extends from theback of the molecule in a wide are followed by an abrupt turn after thelysine 477 residue on the surface near the substrate binding surface.The linker extends as a random coil that is anchored by interactions ofthe side chains of Tyr 452, Pro 465, Phe 470, Gln 474, Pro 475, Lys 477,Val 480 and Tyr 486 to regions on the surface of the catalytic domain.

The starch binding domain is composed of a beta-sandwich of two twistedbeta sheets, tethered at one end by a disulfide bridge between Cys 491and Cys 587 and at the other end, having a series of loops that comprisea binding site for starch connected by long loops. The structure of theTrGA SBD is quite similar to the averaged structure of the AnGA SBDdetermined by NMR (Sorimachi, K., et al., Structure (1997) 5(5): p.647-661) and the SBD of beta amylase from Bacillus cereus (Mikami, B.,et al. Biochemistry (1999) 38(22): p, 7050-61). FIG. 8 shows analignment of the A. niger and TrGA crystal structures including the SBD.When aligned with one or both of these SBD's one loop stands out asbeing highly variable corresponding to residues 537-543 (in A. niger theloop is 554-560 and in B. cereus the loop is 462-465). In the NMRstructure of beta-cyclodextrin, a starch analog complexed to the SBD ofA. niger GA (Sorimachi, et al 1997 supra), the loop shifts substantiallyupon binding to cyclodextrin. Thus, this loop is designated the flexibleloop. This flexible loop forms part of the “binding site 2” (see FIG. 8for this binding site in TrGA). A second binding site was alsoidentified in AnGA (binding site 1), a primary site which sharessimilarities with other carbohydrate binding proteins. Overall,conservation of residues and even side conformations in the binding site1 of these SBDs is very high. The figures demonstrate the interactionsin these binding sites between the SBD and the catalytic domain whichserve to bind to the starch.

Taken together, there appears to be a common pattern for theinteractions between the linker and SBD with the catalytic domain. Theinteraction is in the form of an anchoring side chain that interactswith the surface area of the neighboring domain. In general, the anchorresidue is found on the linker segment. In the case of interactionsbetween the CD and SBD, the anchor residues can be contributed fromeither domain as in the case of residues Ile 43 and Phe 29 which comefrom the CD or residue 592, which comes from the SBD.

Example 13 Model of Acarbose Binding to TrGA

The crystal structure of the TrGA complexed with the inhibitor acarbosehas been determined. Crystals of the complex were obtained by soakingpregrown native TrGA crystals in acarbose. After soaking for 3 days thecrystals were mounted in a seal glass capillary tube and x-raydiffraction was collected with a Rigaku Raxis IV++ image plate detectorto a resolution of 2.0 Å. The coordinates were fitted to a differenceelectron density map. The model was refined to an R-factor of 0.154 withan R-free of 0.201 for a total of 41276 reflection representing all datacollected between 27 and 2.0 Å resolution. The model of the resultingrefined structure is shown in FIG. 9.

Based on the knowledge that the presence of the SBD has an impact onhydrolysis of insoluble starch, it followed that there should be aninteraction of the SBD with larger starch molecules. Thus, the structureof the TrGA was compared with known structures of an acarbose bound CDof AaGA and an SBD from A. niger complexed with beta-cyclodextrin. Thisshowed that the beta-cyclodextrin bound at binding site 2 was close tothe substrate location as indicated by the location of acarbose bound tothe A. awamori CD. Thus, the coordinates of acarbose from the structuremodel of the AaGA (pdb enty1GAI, Aleshin, et al. 1994 supra) werealigned into the TrGA active site. Further, the AnGA SBD structure boundto cyclodextrin (pdb entry 1AC0: Sorimachi, et al 1997 supra) wasaligned. From this, a model was made for acarbose binding to TrGA (seeFIG. 9). The model showed that the SBD would localize the TrGA CD neardisrupted starch, and also prevent the enzyme from diffusing away fromthe substrate while releasing the product from the active site afterhydrolysis. The SBD of TrGA would bind to starch along site 1, and favorlocalization where a disrupted fragment could bind to site 2 within aloose end that points into the catalytic site (the active side for thecatalytic domain). This model shows how the proposed function of theenzyme is contributed by the structure of the SBD and linker. The aminoacid side chains involved in the specific interaction between the CD,the linker and the SBD are specific for Trichoderma reesei GA, however,in other glucoamylases, complementary sequence changes would enablesimilar overall interactions and domain juxtaposition.

Based on this model, sites were identified for which substitutions couldbe made in the TrGA SBD to result in increased stability and/or specificactivity. Thus, two loops that are part of binding site 1 are likelycandidates for alterations to increase or decrease binding to the largerstarch molecule. These are loop 1 (aa 560-570) and loop 2 (aa 523-527).Because the two Trp (tryptophan) residues at amino acids 525 and 572 arelikely involved directly in starch binding, they would not be asconducive to change. However, the underlying residues, including 516-518would be conducive, as would the underlying residues 558-562. The loopfrom residues 570-578 is also a good candidate for alterations. Residues534-541 are part of the binding site 2 which interacts with thecatalytic site on the CD. Thus, these are a good candidate foralterations that may increase or decrease specific activity.

Because of the high structural homology of the TrGA SBD, it is expectedthat beneficial variants found at sites in Trichoderma reesei GA wouldhave similar consequences in Aspergillus awamori and other homologousglucoamylases. Thus, the structure of the TrGA SBD provides a basis forengineering this and related enzymes for altered properties as comparedto a parent glucoamylase. These altered properties may be advantageousfor processes in the generation of fuels based on starch feed stocks.

Various modifications and variations of the described methods and systemof the invention will be apparent to those skilled in the art withoutdeparting from the scope and spirit of the invention. Although theinvention has been described in connection with specific preferredembodiments, it should be understood that the invention as claimedshould not be unduly limited to such specific embodiments. Indeed,various modifications of the described modes for carrying out theinvention which are obvious to those skilled in the art are intended tobe within the scope of the following claims.

TABLE 8 CRYST1 52.185  99.232  121.240  90.00 90.00  90.00 ORIGX1  1.000000  0.000000  0.000000    0.00000 ORIGX2  0.000000  1.000000  0.000000    0.00000 ORIGX3  0.000000  0.000000  1.000000    0.00000 SCALE1  0.019163 −0.000001 −0.000001    0.00000 SCALE2  0.000000  0.010077  0.000000    0.00000 SCALE3  0.000000  0.000000  0.008248    0.00000 ATOM 1 N SER A 1 −30.48530.567 −21.185 1.00 37.11 ATOM 2 CA SER A 1 −30.568 29.350 −20.326 1.0037.00 ATOM 3 CB SER A 1 −31.953 28.707 −20.424 1.00 37.27 ATOM 4 OG SERA 1 −32.137 28.089 −21.695 1.00 40.11 ATOM 5 C SER A 1 −29.519 28.345−20.772 1.00 35.91 ATOM 6 O SER A 1 −29.043 28.415 −21.911 1.00 35.46ATOM 7 N VAL A 2 −29.170 27.425 −19.867 1.00 34.51 ATOM 8 CA VAL A 2−28.302 26.293 −20.179 1.00 33.56 ATOM 9 CB VAL A 2 −28.142 25.339−18.955 1.00 33.84 ATOM 10 CG1 VAL A 2 −27.349 24.103 −19.316 1.00 34.20ATOM 11 CG2 VAL A 2 −27.468 26.057 −17.827 1.00 34.79 ATOM 12 C VAL A 2−28.846 25.506 −21.363 1.00 32.48 ATOM 13 O VAL A 2 −28.086 25.109−22.245 1.00 31.10 ATOM 14 N ASP A 3 −30.160 25.286 −21.381 1.00 31.43ATOM 15 CA ASP A 3 −30.791 24.530 −22.457 1.00 31.38 ATOM 16 CB ASP A 3−32.283 24.323 −22.190 1.00 32.17 ATOM 17 CG ASP A 3 −32.522 23.492−20.943 1.00 35.28 ATOM 18 OD1 ASP A 3 −32.413 22.251 −21.028 1.00 36.80ATOM 19 OD2 ASP A 3 −32.786 24.092 −19.870 1.00 40.63 ATOM 20 C ASP A 3−30.556 25.153 −23.818 1.00 30.59 ATOM 21 O ASP A 3 −30.282 24.446−24.778 1.00 30.19 ATOM 22 N ASP A 4 −30.644 26.477 −23.875 1.00 29.89ATOM 23 CA ASP A 4 −30.369 27.244 −25.083 1.00 29.99 ATOM 24 CB ASP A 4−30.601 28.731 −24.822 1.00 31.12 ATOM 25 CG ASP A 4 −32.088 29.121−24.785 1.00 34.16 ATOM 26 OD1 ASP A 4 −32.991 28.260 −24.925 1.00 36.06ATOM 27 OD2 ASP A 4 −32.340 30.332 −24.608 1.00 39.96 ATOM 28 C ASP A 4−28.925 27.049 −25.579 1.00 28.65 ATOM 29 O ASP A 4 −28.697 26.881−26.770 1.00 28.51 ATOM 30 N PHE A 5 −27.961 27.096 −24.660 1.00 26.74ATOM 31 CA PHE A 5 −26.553 26.860 −24.994 1.00 25.21 ATOM 32 CB PHE A 5−25.666 27.110 −23.764 1.00 25.59 ATOM 33 CG PHE A 5 −24.244 26.646−23.931 1.00 26.03 ATOM 34 CD1 PHE A 5 −23.395 27.259 −24.854 1.00 27.29ATOM 35 CE1 PHE A 5 −22.063 26.823 −25.009 1.00 27.33 ATOM 36 CZ PHE A 5−21.593 25.783 −24.228 1.00 26.77 ATOM 37 CE2 PHE A 5 −22.425 25.181−23.286 1.00 28.42 ATOM 38 CD2 PHE A 5 −23.749 25.617 −23.144 1.00 28.42ATOM 39 C PHE A 5 −26.352 25.438 −25.539 1.00 24.23 ATOM 40 O PHE A 5−25.659 25.244 −26.544 1.00 23.56 ATOM 41 N ILE A 6 −26.974 24.458−24.892 1.00 22.71 ATOM 42 CA ILE A 6 −26.835 23.065 −25.312 1.00 22.36ATOM 43 CB ILE A 6 −27.491 22.106 −24.299 1.00 21.86 ATOM 44 CG1 ILE A 6−26.744 22.181 −22.956 1.00 22.27 ATOM 45 CD1 ILE A 6 −27.384 21.347−21.834 1.00 22.36 ATOM 46 CG2 ILE A 6 −27.571 20.669 −24.848 1.00 21.69ATOM 47 C ILE A 6 −27.388 22.855 −26.723 1.00 22.84 ATOM 48 O ILE A 6−26.753 22.216 −27.573 1.00 21.76 ATOM 49 N SER A 7 −28.556 23.420−26.996 1.00 23.10 ATOM 50 CA SER A 7 −29.146 23.175 −28.309 1.00 23.90ATOM 51 CB SER A 7 −30.627 23.570 −28.320 1.00 25.04 ATOM 52 OG SER A 7−30.717 24.982 −28.282 1.00 30.08 ATOM 53 C SER A 7 −28.340 23.874−29.422 1.00 22.78 ATOM 54 O SER A 7 −28.186 23.337 −30.508 1.00 22.94ATOM 55 N THR A 8 −27.800 25.053 −29.140 1.00 22.50 ATOM 56 CA THR A 8−26.984 25.780 −30.115 1.00 23.05 ATOM 57 CB THR A 8 −26.834 27.247−29.698 1.00 23.65 ATOM 58 OG1 THR A 8 −28.138 27.839 −29.700 1.00 27.60ATOM 59 CG2 THR A 8 −25.939 28.018 −30.660 1.00 26.76 ATOM 60 C THR A 8−25.601 25.159 −30.307 1.00 21.46 ATOM 61 O THR A 8 −25.109 25.051−31.437 1.00 21.38 ATOM 62 N GLU A 9 −24.978 24.768 −29.200 1.00 19.11ATOM 63 CA GLU A 9 −23.596 24.269 −29.243 1.00 18.01 ATOM 64 CB GLU A 9−22.959 24.334 −27.847 1.00 17.76 ATOM 65 CG GLU A 9 −21.449 23.945−27.794 1.00 17.71 ATOM 66 CD GLU A 9 −20.536 24.892 −28.609 1.00 20.86ATOM 67 OE1 GLU A 9 −20.949 26.010 −28.971 1.00 19.89 ATOM 68 OE2 GLU A9 −19.389 24.500 −28.909 1.00 19.22 ATOM 69 C GLU A 9 −23.462 22.846−29.784 1.00 17.77 ATOM 70 O GLU A 9 −22.423 22.505 −30.368 1.00 18.05ATOM 71 N THR A 10 −24.485 22.020 −29.593 1.00 15.87 ATOM 72 CA THR A 10−24.404 20.609 −29.958 1.00 17.31 ATOM 73 CB THR A 10 −25.677 19.823−29.525 1.00 17.46 ATOM 74 OG1 THR A 10 −25.768 19.860 −28.090 1.0017.46 ATOM 75 CG2 THR A 10 −25.616 18.374 −30.037 1.00 18.42 ATOM 76 CTHR A 10 −24.026 20.346 −31.430 1.00 17.40 ATOM 77 O THR A 10 −23.07319.615 −31.682 1.00 17.22 ATOM 78 N PRO A 11 −24.764 20.934 −32.412 1.0018.30 ATOM 79 CA PRO A 11 −24.346 20.649 −33.798 1.00 18.11 ATOM 80 CBPRO A 11 −25.440 21.317 −34.662 1.00 18.57 ATOM 81 CG PRO A 11 −26.09422.310 −33.771 1.00 19.16 ATOM 82 CD PRO A 11 −25.975 21.779 −32.3611.00 18.54 ATOM 83 C PRO A 11 −22.963 21.231 −34.142 1.00 17.81 ATOM 84O PRO A 11 −22.241 20.655 −34.964 1.00 17.74 ATOM 85 N ILE A 12 −22.60122.353 −33.520 1.00 16.85 ATOM 86 CA ILE A 12 −21.279 22.936 −33.7311.00 16.66 ATOM 87 CB ILE A 12 −21.161 24.319 −33.112 1.00 17.25 ATOM 88CG1 ILE A 12 −22.194 25.267 −33.751 1.00 19.25 ATOM 89 CD1 ILE A 12−22.289 26.635 −33.101 1.00 21.45 ATOM 90 CG2 ILE A 12 −19.714 24.855−33.270 1.00 18.75 ATOM 91 C ILE A 12 −20.170 22.023 −33.178 1.00 16.30ATOM 92 O ILE A 12 −19.155 21.798 −33.848 1.00 14.64 ATOM 93 N ALA A 13−20.360 21.527 −31.951 1.00 15.28 ATOM 94 CA ALA A 13 −19.375 20.627−31.304 1.00 15.19 ATOM 95 CB ALA A 13 −19.788 20.332 −29.883 1.00 15.31ATOM 96 C ALA A 13 −19.204 19.326 −32.092 1.00 15.37 ATOM 97 O ALA A 13−18.083 18.834 −32.297 1.00 13.56 ATOM 98 N LEU A 14 −20.320 18.743−32.531 1.00 15.13 ATOM 99 CA LEU A 14 −20.225 17.503 −33.285 1.00 16.06ATOM 100 CB LEU A 14 −21.630 16.921 −33.510 1.00 17.33 ATOM 101 CG LEU A14 −21.689 15.563 −34.212 1.00 20.02 ATOM 102 CD1 LEU A 14 −20.94614.460 −33.471 1.00 23.09 ATOM 103 CD2 LEU A 14 −23.150 15.225 −34.3901.00 21.86 ATOM 104 C LEU A 14 −19.506 17.749 −34.623 1.00 15.61 ATOM105 O LEU A 14 −18.651 16.947 −35.039 1.00 14.82 ATOM 106 N ASN A 15−19.853 18.852 −35.285 1.00 15.30 ATOM 107 CA ASN A 15 −19.236 19.228−36.567 1.00 16.34 ATOM 108 CB ASN A 15 −19.848 20.545 −37.073 1.0016.07 ATOM 109 CG ASN A 15 −19.232 21.010 −38.388 1.00 18.31 ATOM 110OD1 ASN A 15 −19.565 20.487 −39.431 1.00 17.60 ATOM 111 ND2 ASN A 15−18.312 21.987 −38.325 1.00 21.40 ATOM 112 C ASN A 15 −17.736 19.450−36.405 1.00 15.35 ATOM 113 O ASN A 15 −16.926 18.954 −37.198 1.00 15.29ATOM 114 N ASN A 16 −17.385 20.180 −35.355 1.00 14.82 ATOM 115 CA ASN A16 −15.992 20.555 −35.144 1.00 15.27 ATOM 116 CB ASN A 16 −15.872 21.693−34.148 1.00 15.41 ATOM 117 CG ASN A 16 −16.276 23.023 −34.737 1.0016.53 ATOM 118 OD1 ASN A 16 −16.517 23.136 −35.954 1.00 18.08 ATOM 119ND2 ASN A 16 −16.326 24.050 −33.896 1.00 16.35 ATOM 120 C ASN A 16−15.159 19.362 −34.723 1.00 14.91 ATOM 121 O ASN A 16 −13.975 19.261−35.099 1.00 15.34 ATOM 122 N LEU A 17 −15.771 18.460 −33.956 1.00 14.29ATOM 123 CA LEU A 17 −15.114 17.191 −33.610 1.00 13.90 ATOM 124 CB LEU A17 −16.003 16.346 −32.672 1.00 13.94 ATOM 125 CG LEU A 17 −15.351 15.065−32.133 1.00 16.81 ATOM 126 CD1 LEU A 17 −15.933 14.708 −30.779 1.0020.06 ATOM 127 CD2 LEU A 17 −15.484 13.880 −33.097 1.00 19.31 ATOM 128 CLEU A 17 −14.763 16.409 −34.880 1.00 14.06 ATOM 129 O LEU A 17 −13.61315.957 −35.073 1.00 12.69 ATOM 130 N LEU A 18 −15.774 16.215 −35.7301.00 13.19 ATOM 131 CA LEU A 18 −15.589 15.441 −36.957 1.00 14.25 ATOM132 CB LEU A 18 −16.952 15.027 −37.545 1.00 13.56 ATOM 133 CG LEU A 18−17.717 14.013 −36.684 1.00 16.49 ATOM 134 CD1 LEU A 18 −19.171 13.874−37.165 1.00 16.33 ATOM 135 CD2 LEU A 18 −17.020 12.647 −36.655 1.0018.51 ATOM 136 C LEU A 18 −14.703 16.132 −38.007 1.00 13.49 ATOM 137 OLEU A 18 −14.083 15.435 −38.820 1.00 14.69 ATOM 138 N CYS A 19 −14.61317.462 −37.964 1.00 13.01 ATOM 139 CA CYS A 19 −13.629 18.223 −38.7601.00 13.22 ATOM 140 CB CYS A 19 −13.796 19.738 −38.556 1.00 14.20 ATOM141 SG CYS A 19 −15.125 20.407 −39.642 1.00 16.22 ATOM 142 C CYS A 19−12.182 17.808 −38.450 1.00 13.86 ATOM 143 O CYS A 19 −11.278 18.043−39.259 1.00 13.42 ATOM 144 N ASN A 20 −11.968 17.219 −37.272 1.00 13.21ATOM 145 CA ASN A 20 −10.594 16.850 −36.830 1.00 13.62 ATOM 146 CB ASN A20 −10.394 17.184 −35.324 1.00 13.52 ATOM 147 CG ASN A 20 −10.242 18.687−35.055 1.00 16.17 ATOM 148 OD1 ASN A 20 −10.035 19.119 −33.897 1.0017.34 ATOM 149 ND2 ASN A 20 −10.343 19.486 −36.090 1.00 11.87 ATOM 150 CASN A 20 −10.262 15.381 −37.116 1.00 13.99 ATOM 151 O ASN A 20 −9.23814.857 −36.646 1.00 14.28 ATOM 152 N VAL A 21 −11.123 14.705 −37.8751.00 13.41 ATOM 153 CA VAL A 21 −10.923 13.287 −38.167 1.00 14.20 ATOM154 CB VAL A 21 −12.177 12.448 −37.827 1.00 14.30 ATOM 155 CG1 VAL A 21−11.953 10.971 −38.189 1.00 15.30 ATOM 156 CG2 VAL A 21 −12.517 12.553−36.312 1.00 14.17 ATOM 157 C VAL A 21 −10.551 13.136 −39.644 1.00 14.35ATOM 158 O VAL A 21 −11.255 13.642 −40.491 1.00 15.68 ATOM 159 N GLY A22 −9.461 12.449 −39.953 1.00 15.67 ATOM 160 CA GLY A 22 −9.061 12.300−41.377 1.00 15.70 ATOM 161 C GLY A 22 −9.843 11.182 −42.060 1.00 17.34ATOM 162 O GLY A 22 −10.453 10.358 −41.397 1.00 17.15 ATOM 163 N PRO A23 −9.806 11.117 −43.404 1.00 18.42 ATOM 164 CA PRO A 23 −9.009 11.946−44.278 1.00 18.20 ATOM 165 CB PRO A 23 −8.716 10.990 −45.446 1.00 18.64ATOM 166 CG PRO A 23 −9.983 10.171 −45.560 1.00 18.81 ATOM 167 CD PRO A23 −10.568 10.092 −44.153 1.00 18.59 ATOM 168 C PRO A 23 −9.761 13.182−44.753 1.00 19.05 ATOM 169 O PRO A 23 −9.183 14.055 −45.426 1.00 19.36ATOM 170 N ASP A 24 −11.034 13.288 −44.385 1.00 18.76 ATOM 171 CA ASP A24 −11.878 14.305 −44.996 1.00 19.39 ATOM 172 CB ASP A 24 −13.015 13.636−45.781 1.00 20.87 ATOM 173 CG ASP A 24 −13.920 12.784 −44.913 1.0024.34 ATOM 174 OD1 ASP A 24 −13.502 12.291 −43.839 1.00 27.70 ATOM 175OD2 ASP A 24 −15.079 12.580 −45.330 1.00 28.83 ATOM 176 C ASP A 24−12.452 15.372 −44.061 1.00 18.08 ATOM 177 O ASP A 24 −13.208 16.245−44.509 1.00 17.78 ATOM 178 N GLY A 25 −12.100 15.331 −42.775 1.00 16.65ATOM 179 CA GLY A 25 −12.634 16.343 −41.852 1.00 16.02 ATOM 180 C GLY A25 −12.152 17.718 −42.292 1.00 15.70 ATOM 181 O GLY A 25 −11.033 17.849−42.811 1.00 16.22 ATOM 182 N CYS A 26 −12.979 18.752 −42.086 1.00 15.10ATOM 183 CA CYS A 26 −12.698 20.078 −42.637 1.00 15.46 ATOM 184 CB CYS A26 −13.899 21.037 −42.475 1.00 15.47 ATOM 185 SG CYS A 26 −14.147 21.739−40.786 1.00 16.91 ATOM 186 C CYS A 26 −11.407 20.731 −42.116 1.00 15.65ATOM 187 O CYS A 26 −10.896 21.643 −42.763 1.00 15.80 ATOM 188 N ARG A27 −10.879 20.259 −40.973 1.00 15.02 ATOM 189 CA ARG A 27 −9.615 20.808−40.443 1.00 14.56 ATOM 190 CB ARG A 27 −9.819 21.480 −39.066 1.00 15.00ATOM 191 CG ARG A 27 −10.695 22.728 −39.164 1.00 15.15 ATOM 192 CD ARG A27 −10.826 23.551 −37.888 1.00 14.30 ATOM 193 NE ARG A 27 −11.874 24.566−38.080 1.00 15.05 ATOM 194 CZ ARG A 27 −13.160 24.420 −37.761 1.0017.96 ATOM 195 NH1 ARG A 27 −13.623 23.293 −37.211 1.00 17.37 ATOM 196NH2 ARG A 27 −14.009 25.415 −38.025 1.00 19.55 ATOM 197 C ARG A 27−8.489 19.776 −40.394 1.00 15.49 ATOM 198 O ARG A 27 −7.389 20.079−39.888 1.00 15.40 ATOM 199 N ALA A 28 −8.768 18.577 −40.910 1.00 15.17ATOM 200 CA ALA A 28 −7.805 17.484 −40.988 1.00 16.06 ATOM 201 CB ALA A28 −8.163 16.374 −39.975 1.00 15.52 ATOM 202 C ALA A 28 −7.744 16.913−42.394 1.00 16.96 ATOM 203 O ALA A 28 −7.453 15.730 −42.581 1.00 17.60ATOM 204 N PHE A 29 −8.028 17.756 −43.380 1.00 17.45 ATOM 205 CA PHE A29 −8.188 17.272 −44.744 1.00 18.68 ATOM 206 CB PHE A 29 −8.728 18.376−45.636 1.00 19.45 ATOM 207 CG PHE A 29 −9.299 17.864 −46.919 1.00 20.86ATOM 208 CD1 PHE A 29 −8.515 17.827 −48.071 1.00 23.76 ATOM 209 CE1 PHEA 29 −9.042 17.343 −49.267 1.00 25.46 ATOM 210 CZ PHE A 29 −10.35716.889 −49.318 1.00 22.85 ATOM 211 CE2 PHE A 29 −11.151 16.924 −48.1801.00 24.78 ATOM 212 CD2 PHE A 29 −10.611 17.408 −46.973 1.00 22.71 ATOM213 C PHE A 29 −6.853 16.783 −45.296 1.00 19.10 ATOM 214 O PHE A 29−5.862 17.501 −45.224 1.00 19.40 ATOM 215 N GLY A 30 −6.830 15.558−45.816 1.00 18.73 ATOM 216 CA GLY A 30 −5.603 15.008 −46.398 1.00 19.00ATOM 217 C GLY A 30 −4.717 14.307 −45.399 1.00 19.69 ATOM 218 O GLY A 30−3.657 13.809 −45.768 1.00 19.61 ATOM 219 N THR A 31 −5.133 14.255−44.123 1.00 18.86 ATOM 220 CA THR A 31 −4.450 13.384 −43.165 1.00 19.14ATOM 221 CB THR A 31 −4.846 13.689 −41.689 1.00 18.79 ATOM 222 OG1 THR A31 −6.265 13.579 −41.559 1.00 18.61 ATOM 223 CG2 THR A 31 −4.410 15.106−41.262 1.00 16.47 ATOM 224 C THR A 31 −4.812 11.925 −43.498 1.00 19.11ATOM 225 O THR A 31 −5.713 11.661 −44.313 1.00 19.69 ATOM 226 N SER A 32−4.107 10.982 −42.881 1.00 19.74 ATOM 227 CA SER A 32 −4.367 9.554−43.094 1.00 20.00 ATOM 228 CB SER A 32 −3.411 8.722 −42.248 1.00 20.73ATOM 229 OG SER A 32 −2.064 8.973 −42.612 1.00 21.56 ATOM 230 C SER A 32−5.806 9.217 −42.704 1.00 20.57 ATOM 231 O SER A 32 −6.334 9.778 −41.7321.00 20.70 ATOM 232 N ALA A 33 −6.443 8.319 −43.452 1.00 19.94 ATOM 233CA ALA A 33 −7.768 7.823 −43.068 1.00 19.61 ATOM 234 CB ALA A 33 −8.2326.729 −44.035 1.00 19.31 ATOM 235 C ALA A 33 −7.764 7.285 −41.637 1.0019.10 ATOM 236 O ALA A 33 −6.906 6.482 −41.264 1.00 19.49 ATOM 237 N GLYA 34 −8.742 7.719 −40.856 1.00 17.74 ATOM 238 CA GLY A 34 −8.878 7.282−39.473 1.00 18.31 ATOM 239 C GLY A 34 −7.988 8.020 −38.473 1.00 18.48ATOM 240 O GLY A 34 −8.050 7.739 −37.271 1.00 19.07 ATOM 241 N ALA A 35−7.173 8.959 −38.937 1.00 17.05 ATOM 242 CA ALA A 35 −6.329 9.723−38.000 1.00 17.17 ATOM 243 CB ALA A 35 −5.167 10.376 −38.730 1.00 17.10ATOM 244 C ALA A 35 −7.173 10.784 −37.271 1.00 16.55 ATOM 245 O ALA A 35−8.174 11.271 −37.808 1.00 17.35 ATOM 246 N VAL A 36 −6.793 11.130−36.051 1.00 15.39 ATOM 247 CA VAL A 36 −7.490 12.198 −35.328 1.00 14.41ATOM 248 CB VAL A 36 −8.142 11.687 −34.031 1.00 15.02 ATOM 249 CG1 VAL A36 −8.903 12.828 −33.349 1.00 16.72 ATOM 250 CG2 VAL A 36 −9.081 10.520−34.336 1.00 16.45 ATOM 251 C VAL A 36 −6.407 13.201 −34.944 1.00 14.36ATOM 252 O VAL A 36 −5.421 12.816 −34.311 1.00 14.44 ATOM 253 N ILE A 37−6.566 14.454 −35.331 1.00 13.68 ATOM 254 CA ILE A 37 −5.614 15.470−34.893 1.00 13.67 ATOM 255 CB ILE A 37 −5.528 16.687 −35.849 1.00 13.66ATOM 256 CG1 ILE A 37 −6.847 17.486 −35.901 1.00 14.31 ATOM 257 CD1 ILEA 37 −6.773 18.712 −36.864 1.00 14.21 ATOM 258 CG2 ILE A 37 −5.15816.214 −37.260 1.00 14.62 ATOM 259 C ILE A 37 −6.041 15.908 −33.505 1.0013.27 ATOM 260 O ILE A 37 −7.235 16.011 −33.224 1.00 12.99 ATOM 261 NALA A 38 −5.081 16.159 −32.630 1.00 13.03 ATOM 262 CA ALA A 38 −5.44516.697 −31.333 1.00 12.81 ATOM 263 CB ALA A 38 −4.235 16.680 −30.3771.00 12.73 ATOM 264 C ALA A 38 −6.046 18.122 −31.497 1.00 12.45 ATOM 265O ALA A 38 −6.939 18.503 −30.775 1.00 12.23 ATOM 266 N SER A 39 −5.55518.870 −32.482 1.00 12.90 ATOM 267 CA SER A 39 −5.973 20.246 −32.7691.00 12.85 ATOM 268 CB SER A 39 −5.512 21.211 −31.657 1.00 12.63 ATOM269 OG SER A 39 −5.312 22.563 −32.108 1.00 12.57 ATOM 270 C SER A 39−5.281 20.593 −34.090 1.00 13.33 ATOM 271 O SER A 39 −4.215 20.043−34.376 1.00 13.48 ATOM 272 N PRO A 40 −5.880 21.500 −34.885 1.00 13.12ATOM 273 CA PRO A 40 −5.248 21.999 −36.108 1.00 13.76 ATOM 274 CB PRO A40 −6.407 22.689 −36.860 1.00 14.41 ATOM 275 CG PRO A 40 −7.386 23.045−35.797 1.00 14.32 ATOM 276 CD PRO A 40 −7.223 22.081 −34.665 1.00 13.18ATOM 277 C PRO A 40 −4.126 23.010 −35.860 1.00 14.27 ATOM 278 O PRO A 40−3.474 23.420 −36.824 1.00 14.43 ATOM 279 N SER A 41 −3.864 23.381−34.599 1.00 13.42 ATOM 280 CA SER A 41 −2.799 24.336 −34.318 1.00 14.56ATOM 281 CB SER A 41 −2.788 24.817 −32.840 1.00 14.40 ATOM 282 OG SER A41 −3.962 25.574 −32.534 1.00 16.91 ATOM 283 C SER A 41 −1.446 23.713−34.676 1.00 14.51 ATOM 284 O SER A 41 −1.123 22.626 −34.218 1.00 13.96ATOM 285 N THR A 42 −0.650 24.433 −35.470 1.00 15.63 ATOM 286 CA THR A42 0.652 23.924 −35.919 1.00 16.17 ATOM 287 CB THR A 42 0.750 23.997−37.458 1.00 17.02 ATOM 288 OG1 THR A 42 0.267 25.283 −37.890 1.00 17.03ATOM 289 CG2 THR A 42 −0.110 22.906 −38.078 1.00 16.03 ATOM 290 C THR A42 1.814 24.732 −35.322 1.00 17.44 ATOM 291 O THR A 42 2.967 24.297−35.382 1.00 17.10 ATOM 292 N ILE A 43 1.509 25.913 −34.787 1.00 18.37ATOM 293 CA ILE A 43 2.510 26.786 −34.171 1.00 20.62 ATOM 294 CB ILE A43 2.923 27.952 −35.114 1.00 20.73 ATOM 295 CG1 ILE A 43 3.550 27.428−36.411 1.00 21.88 ATOM 296 CD1 ILE A 43 3.788 28.507 −37.508 1.00 22.99ATOM 297 CG2 ILE A 43 3.895 28.910 −34.409 1.00 21.41 ATOM 298 C ILE A43 1.908 27.395 −32.935 1.00 21.00 ATOM 299 O ILE A 43 0.796 27.921−32.995 1.00 21.76 ATOM 300 N ASP A 44 2.683 27.470 −31.874 1.00 21.61ATOM 301 CA ASP A 44 2.237 27.975 −30.572 1.00 23.04 ATOM 302 CB ASP A44 2.408 29.506 −30.492 1.00 24.75 ATOM 303 CG ASP A 44 2.170 30.064−29.098 1.00 31.28 ATOM 304 OD1 ASP A 44 2.362 29.340 −28.094 1.00 37.92ATOM 305 OD2 ASP A 44 1.766 31.260 −28.997 1.00 40.00 ATOM 306 C ASP A44 0.782 27.608 −30.196 1.00 21.65 ATOM 307 O ASP A 44 −0.046 28.502−29.981 1.00 22.69 ATOM 308 N PRO A 45 0.441 26.449 −29.805 1.00 19.86ATOM 309 CA PRO A 45 1.356 25.320 −29.775 1.00 18.66 ATOM 310 CB PRO A45 0.883 24.549 −28.549 1.00 18.40 ATOM 311 CG PRO A 45 −0.653 24.763−28.586 1.00 18.13 ATOM 312 CD PRO A 45 −0.899 26.066 −29.318 1.00 20.04ATOM 313 C PRO A 45 1.253 24.454 −31.026 1.00 17.74 ATOM 314 O PRO A 450.368 24.652 −31.858 1.00 17.36 ATOM 315 N ASP A 46 2.178 23.512 −31.1601.00 15.95 ATOM 316 CA ASP A 46 2.124 22.573 −32.275 1.00 14.75 ATOM 317CB ASP A 46 3.551 22.255 −32.738 1.00 14.59 ATOM 318 CG ASP A 46 3.60121.161 −33.818 1.00 16.17 ATOM 319 OD1 ASP A 46 2.543 20.787 −34.3891.00 15.61 ATOM 320 OD2 ASP A 46 4.712 20.641 −34.054 1.00 20.18 ATOM321 C ASP A 46 1.436 21.303 −31.748 1.00 13.83 ATOM 322 O ASP A 46 2.08120.489 −31.089 1.00 13.59 ATOM 323 N TYR A 47 0.126 21.165 −31.992 1.0011.86 ATOM 324 CA TYR A 47 −0.621 19.975 −31.580 1.00 12.11 ATOM 325 CBTYR A 47 −1.895 20.387 −30.854 1.00 11.69 ATOM 326 CG TYR A 47 −1.77320.722 −29.377 1.00 12.59 ATOM 327 CD1 TYR A 47 −0.589 21.236 −28.8271.00 13.54 ATOM 328 CE1 TYR A 47 −0.524 21.586 −27.462 1.00 12.81 ATOM329 CZ TYR A 47 −1.652 21.407 −26.673 1.00 13.40 ATOM 330 OH TYR A 47−1.620 21.755 −25.354 1.00 13.08 ATOM 331 CE2 TYR A 47 −2.825 20.887−27.208 1.00 12.02 ATOM 332 CD2 TYR A 47 −2.876 20.540 −28.532 1.0012.76 ATOM 333 C TYR A 47 −0.994 19.090 −32.772 1.00 11.46 ATOM 334 OTYR A 47 −1.885 18.239 −32.692 1.00 11.66 ATOM 335 N TYR A 48 −0.31619.301 −33.893 1.00 12.26 ATOM 336 CA TYR A 48 −0.697 18.639 −35.1321.00 12.80 ATOM 337 CB TYR A 48 −0.323 19.509 −36.348 1.00 12.75 ATOM338 CG TYR A 48 −1.134 19.146 −37.569 1.00 13.21 ATOM 339 CD1 TYR A 48−2.492 19.482 −37.652 1.00 14.46 ATOM 340 CE1 TYR A 48 −3.254 19.124−38.767 1.00 15.86 ATOM 341 CZ TYR A 48 −2.643 18.453 −39.823 1.00 14.62ATOM 342 OH TYR A 48 −3.390 18.106 −40.936 1.00 16.20 ATOM 343 CE2 TYR A48 −1.295 18.086 −39.756 1.00 15.86 ATOM 344 CD2 TYR A 48 −0.543 18.456−38.638 1.00 13.44 ATOM 345 C TYR A 48 −0.072 17.245 −35.187 1.00 13.47ATOM 346 O TYR A 48 0.877 16.986 −35.940 1.00 13.95 ATOM 347 N TYR A 49−0.592 16.360 −34.338 1.00 13.13 ATOM 348 CA TYR A 49 −0.131 14.987−34.171 1.00 13.51 ATOM 349 CB TYR A 49 0.887 14.842 −33.009 1.00 13.11ATOM 350 CG TYR A 49 2.133 15.662 −33.216 1.00 13.90 ATOM 351 CD1 TYR A49 3.193 15.174 −33.996 1.00 13.54 ATOM 352 CE1 TYR A 49 4.354 15.964−34.216 1.00 13.41 ATOM 353 CZ TYR A 49 4.419 17.225 −33.665 1.00 14.69ATOM 354 OH TYR A 49 5.511 18.016 −33.883 1.00 17.21 ATOM 355 CE2 TYR A49 3.365 17.737 −32.906 1.00 13.49 ATOM 356 CD2 TYR A 49 2.227 16.952−32.698 1.00 13.78 ATOM 357 C TYR A 49 −1.349 14.181 −33.783 1.00 13.93ATOM 358 O TYR A 49 −2.390 14.759 −33.406 1.00 13.00 ATOM 359 N MET A 50−1.203 12.857 −33.839 1.00 13.66 ATOM 360 CA MET A 50 −2.241 11.940−33.365 1.00 14.56 ATOM 361 CB MET A 50 −2.447 10.822 −34.381 1.00 15.21ATOM 362 CG MET A 50 −3.532 9.811 −33.947 1.00 15.64 ATOM 363 SD MET A50 −3.996 8.804 −35.361 1.00 19.52 ATOM 364 CE MET A 50 −5.204 7.742−34.566 1.00 17.12 ATOM 365 C MET A 50 −1.797 11.323 −32.060 1.00 14.38ATOM 366 O MET A 50 −0.806 10.583 −32.024 1.00 13.80 ATOM 367 N TRP A 51−2.528 11.608 −30.984 1.00 13.47 ATOM 368 CA TRP A 51 −2.265 10.965−29.720 1.00 13.13 ATOM 369 CB TRP A 51 −2.598 11.930 −28.585 1.00 12.85ATOM 370 CG TRP A 51 −1.478 12.809 −28.116 1.00 13.64 ATOM 371 CD1 TRP A51 −0.671 12.604 −27.011 1.00 13.49 ATOM 372 NE1 TRP A 51 0.211 13.657−26.864 1.00 12.36 ATOM 373 CE2 TRP A 51 −0.023 14.573 −27.858 1.0011.83 ATOM 374 CD2 TRP A 51 −1.076 14.065 −28.674 1.00 13.12 ATOM 375CE3 TRP A 51 −1.506 14.825 −29.772 1.00 11.07 ATOM 376 CZ3 TRP A 51−0.859 16.061 −30.035 1.00 12.87 ATOM 377 CH2 TRP A 51 0.193 16.522−29.218 1.00 13.24 ATOM 378 CZ2 TRP A 51 0.618 15.806 −28.127 1.00 12.61ATOM 379 C TRP A 51 −3.136 9.732 −29.575 1.00 13.35 ATOM 380 O TRP A 51−4.322 9.769 −29.907 1.00 12.89 ATOM 381 N THR A 52 −2.576 8.652 −29.0241.00 13.20 ATOM 382 CA THR A 52 −3.386 7.462 −28.753 1.00 13.02 ATOM 383CB THR A 52 −2.520 6.300 −28.235 1.00 13.66 ATOM 384 OG1 THR A 52 −1.5535.999 −29.246 1.00 15.07 ATOM 385 CG2 THR A 52 −3.341 5.026 −27.952 1.0012.21 ATOM 386 C THR A 52 −4.533 7.807 −27.800 1.00 12.48 ATOM 387 O THRA 52 −5.670 7.402 −28.034 1.00 12.78 ATOM 388 N ARG A 53 −4.224 8.556−26.747 1.00 12.03 ATOM 389 CA ARG A 53 −5.238 8.868 −25.737 1.00 11.89ATOM 390 CB ARG A 53 −4.607 9.570 −24.545 1.00 11.46 ATOM 391 CG ARG A53 −5.611 10.330 −23.618 1.00 13.19 ATOM 392 CD ARG A 53 −4.896 10.881−22.375 1.00 11.14 ATOM 393 NE ARG A 53 −3.793 11.694 −22.819 1.00 12.52ATOM 394 CZ ARG A 53 −2.509 11.330 −22.769 1.00 13.67 ATOM 395 NH1 ARG A53 −2.148 10.182 −22.180 1.00 13.97 ATOM 396 NH2 ARG A 53 −1.590 12.151−23.270 1.00 13.05 ATOM 397 C ARG A 53 −6.395 9.709 −26.319 1.00 12.45ATOM 398 O ARG A 53 −7.558 9.289 −26.244 1.00 11.74 ATOM 399 N ASP A 54−6.090 10.885 −26.874 1.00 11.73 ATOM 400 CA ASP A 54 −7.169 11.747−27.385 1.00 11.90 ATOM 401 CB ASP A 54 −6.638 13.018 −28.053 1.00 12.25ATOM 402 CG ASP A 54 −5.794 13.879 −27.120 1.00 13.97 ATOM 403 OD1 ASP A54 −4.983 13.332 −26.354 1.00 13.57 ATOM 404 OD2 ASP A 54 −5.910 15.110−27.215 1.00 13.88 ATOM 405 C ASP A 54 −8.002 11.005 −28.420 1.00 12.00ATOM 406 O ASP A 54 −9.236 11.138 −28.454 1.00 10.97 ATOM 407 N SER A 55−7.334 10.250 −29.297 1.00 11.19 ATOM 408 CA SER A 55 −8.034 9.544−30.388 1.00 12.36 ATOM 409 CB SER A 55 −7.017 8.901 −31.340 1.00 13.05ATOM 410 OG SER A 55 −6.171 9.930 −31.882 1.00 14.23 ATOM 411 C SER A 55−8.996 8.489 −29.838 1.00 12.57 ATOM 412 O SER A 55 −10.130 8.348−30.327 1.00 12.76 ATOM 413 N ALA A 56 −8.556 7.764 −28.819 1.00 12.60ATOM 414 CA ALA A 56 −9.373 6.718 −28.218 1.00 13.25 ATOM 415 CB ALA A56 −8.517 5.830 −27.329 1.00 12.73 ATOM 416 C ALA A 56 −10.551 7.301−27.415 1.00 13.85 ATOM 417 O ALA A 56 −11.640 6.723 −27.409 1.00 14.51ATOM 418 N LEU A 57 −10.328 8.420 −26.723 1.00 14.23 ATOM 419 CA LEU A57 −11.417 9.059 −25.954 1.00 13.95 ATOM 420 CB LEU A 57 −10.891 10.186−25.060 1.00 14.45 ATOM 421 CG LEU A 57 −10.088 9.751 −23.834 1.00 14.89ATOM 422 CD1 LEU A 57 −9.507 11.013 −23.161 1.00 16.19 ATOM 423 CD2 LEUA 57 −10.919 8.911 −22.867 1.00 16.02 ATOM 424 C LEU A 57 −12.483 9.609−26.886 1.00 13.92 ATOM 425 O LEU A 57 −13.685 9.488 −26.627 1.00 13.70ATOM 426 N VAL A 58 −12.027 10.199 −27.975 1.00 13.15 ATOM 427 CA VAL A58 −12.920 10.751 −28.989 1.00 15.20 ATOM 428 CB VAL A 58 −12.133 11.605−30.031 1.00 14.52 ATOM 429 CG1 VAL A 58 −12.970 11.861 −31.302 1.0017.86 ATOM 430 CG2 VAL A 58 −11.704 12.954 −29.393 1.00 15.79 ATOM 431 CVAL A 58 −13.704 9.624 −29.655 1.00 15.20 ATOM 432 O VAL A 58 −14.9309.718 −29.784 1.00 15.30 ATOM 433 N PHE A 59 −13.026 8.553 −30.058 1.0015.02 ATOM 434 CA PHE A 59 −13.766 7.477 −30.713 1.00 15.23 ATOM 435 CBPHE A 59 −12.882 6.601 −31.582 1.00 15.78 ATOM 436 CG PHE A 59 −12.8597.058 −33.003 1.00 15.10 ATOM 437 CD1 PHE A 59 −11.872 7.927 −33.4441.00 16.45 ATOM 438 CE1 PHE A 59 −11.861 8.401 −34.768 1.00 19.37 ATOM439 CZ PHE A 59 −12.876 8.026 −35.644 1.00 16.44 ATOM 440 CE2 PHE A 59−13.901 7.165 −35.186 1.00 16.90 ATOM 441 CD2 PHE A 59 −13.895 6.709−33.882 1.00 16.17 ATOM 442 C PHE A 59 −14.674 6.681 −29.785 1.00 15.69ATOM 443 O PHE A 59 −15.699 6.175 −30.220 1.00 15.46 ATOM 444 N LYS A 60−14.321 6.586 −28.510 1.00 15.65 ATOM 445 CA LYS A 60 −15.257 5.994−27.552 1.00 16.61 ATOM 446 CB LYS A 60 −14.661 5.954 −26.144 1.00 16.44ATOM 447 CG LYS A 60 −15.626 5.363 −25.059 1.00 17.65 ATOM 448 CD LYS A60 −16.174 3.992 −25.433 1.00 18.35 ATOM 449 CE LYS A 60 −16.738 3.234−24.199 1.00 19.79 ATOM 450 NZ LYS A 60 −17.819 3.976 −23.512 1.00 18.40ATOM 451 C LYS A 60 −16.577 6.779 −27.579 1.00 16.72 ATOM 452 O LYS A 60−17.663 6.182 −27.681 1.00 17.08 ATOM 453 N ASN A 61 −16.487 8.101−27.508 1.00 16.77 ATOM 454 CA ASN A 61 −17.680 8.948 −27.628 1.00 18.06ATOM 455 CB ASN A 61 −17.278 10.424 −27.573 1.00 19.41 ATOM 456 CG ASN A61 −18.465 11.375 −27.643 1.00 22.93 ATOM 457 OD1 ASN A 61 −19.58511.057 −27.231 1.00 30.05 ATOM 458 ND2 ASN A 61 −18.206 12.568 −28.1301.00 29.54 ATOM 459 C ASN A 61 −18.480 8.659 −28.907 1.00 17.28 ATOM 460O ASN A 61 −19.697 8.475 −28.852 1.00 18.11 ATOM 461 N LEU A 62 −17.7998.647 −30.056 1.00 16.54 ATOM 462 CA LEU A 62 −18.460 8.379 −31.334 1.0016.19 ATOM 463 CB LEU A 62 −17.479 8.572 −32.499 1.00 16.85 ATOM 464 CGLEU A 62 −17.047 10.027 −32.697 1.00 18.47 ATOM 465 CD1 LEU A 62 −16.11810.153 −33.916 1.00 20.38 ATOM 466 CD2 LEU A 62 −18.263 10.925 −32.8371.00 19.93 ATOM 467 C LEU A 62 −19.089 6.991 −31.371 1.00 16.01 ATOM 468O LEU A 62 −20.225 6.833 −31.842 1.00 15.98 ATOM 469 N ILE A 63 −18.3875.998 −30.831 1.00 15.67 ATOM 470 CA ILE A 63 −18.910 4.628 −30.810 1.0015.86 ATOM 471 CB ILE A 63 −17.803 3.610 −30.372 1.00 15.88 ATOM 472 CG1ILE A 63 −16.756 3.466 −31.478 1.00 14.98 ATOM 473 CD1 ILE A 63 −15.3752.976 −30.966 1.00 15.62 ATOM 474 CG2 ILE A 63 −18.398 2.251 −30.0161.00 15.96 ATOM 475 C ILE A 63 −20.156 4.538 −29.920 1.00 16.39 ATOM 476O ILE A 63 −21.137 3.854 −30.272 1.00 16.90 ATOM 477 N ASP A 64 −20.1295.242 −28.796 1.00 16.51 ATOM 478 CA ASP A 64 −21.299 5.324 −27.922 1.0017.76 ATOM 479 CB ASP A 64 −20.953 6.022 −26.594 1.00 17.81 ATOM 480 CGASP A 64 −20.089 5.164 −25.682 1.00 17.84 ATOM 481 OD1 ASP A 64 −19.8833.944 −25.963 1.00 18.57 ATOM 482 OD2 ASP A 64 −19.595 5.699 −24.6591.00 20.95 ATOM 483 C ASP A 64 −22.492 5.982 −28.617 1.00 18.64 ATOM 484O ASP A 64 −23.617 5.493 −28.507 1.00 20.85 ATOM 485 N ARG A 65 −22.2627.070 −29.348 1.00 19.57 ATOM 486 CA ARG A 65 −23.341 7.750 −30.097 1.0020.59 ATOM 487 CB ARG A 65 −22.823 9.046 −30.733 1.00 20.62 ATOM 488 CGARG A 65 −22.465 10.083 −29.693 1.00 25.00 ATOM 489 CD ARG A 65 −22.01011.385 −30.324 1.00 28.44 ATOM 490 NE ARG A 65 −23.106 12.071 −30.9901.00 31.14 ATOM 491 CZ ARG A 65 −23.968 12.878 −30.373 1.00 32.75 ATOM492 NH1 ARG A 65 −23.873 13.095 −29.060 1.00 32.10 ATOM 493 NH2 ARG A 65−24.928 13.459 −31.080 1.00 32.31 ATOM 494 C ARG A 65 −23.907 6.841−31.184 1.00 20.83 ATOM 495 O ARG A 65 −25.129 6.711 −31.357 1.00 20.48ATOM 496 N PHE A 66 −22.998 6.213 −31.910 1.00 20.52 ATOM 497 CA PHE A66 −23.340 5.271 −32.966 1.00 21.42 ATOM 498 CB PHE A 66 −22.046 4.778−33.604 1.00 21.97 ATOM 499 CG PHE A 66 −22.224 3.603 −34.520 1.00 21.97ATOM 500 CD1 PHE A 66 −22.601 3.791 −35.844 1.00 23.23 ATOM 501 CE1 PHEA 66 −22.768 2.690 −36.699 1.00 22.87 ATOM 502 CZ PHE A 66 −22.552 1.409−36.221 1.00 22.60 ATOM 503 CE2 PHE A 66 −22.165 1.216 −34.895 1.0023.74 ATOM 504 CD2 PHE A 66 −22.006 2.309 −34.054 1.00 23.07 ATOM 505 CPHE A 66 −24.152 4.084 −32.415 1.00 21.98 ATOM 506 O PHE A 66 −25.0403.551 −33.099 1.00 21.80 ATOM 507 N THR A 67 −23.831 3.654 −31.195 1.0022.48 ATOM 508 CA THR A 67 −24.546 2.537 −30.576 1.00 23.79 ATOM 509 CBTHR A 67 −23.809 1.999 −29.333 1.00 23.68 ATOM 510 OG1 THR A 67 −22.5511.439 −29.745 1.00 23.93 ATOM 511 CG2 THR A 67 −24.613 0.881 −28.6531.00 23.90 ATOM 512 C THR A 67 −25.992 2.925 −30.258 1.00 24.77 ATOM 513O THR A 67 −26.893 2.090 −30.349 1.00 25.31 ATOM 514 N GLU A 68 −26.2074.189 −29.916 1.00 25.62 ATOM 515 CA GLU A 68 −27.540 4.688 −29.616 1.0027.41 ATOM 516 CB GLU A 68 −27.466 6.038 −28.894 1.00 28.13 ATOM 517 CGGLU A 68 −26.997 5.951 −27.446 1.00 32.86 ATOM 518 CD GLU A 68 −28.0955.487 −26.468 1.00 38.33 ATOM 519 OE1 GLU A 68 −29.241 5.982 −26.5421.00 40.42 ATOM 520 OE2 GLU A 68 −27.799 4.633 −25.607 1.00 42.48 ATOM521 C GLU A 68 −28.418 4.784 −30.873 1.00 27.86 ATOM 522 O GLU A 68−29.602 4.429 −30.845 1.00 28.00 ATOM 523 N THR A 69 −27.833 5.260−31.968 1.00 27.32 ATOM 524 CA THR A 69 −28.540 5.373 −33.241 1.00 27.32ATOM 525 CB THR A 69 −29.113 6.792 −33.451 1.00 27.49 ATOM 526 OG1 THR A69 −29.922 7.153 −32.334 1.00 30.86 ATOM 527 CG2 THR A 69 −29.945 6.843−34.719 1.00 29.06 ATOM 528 C THR A 69 −27.563 5.133 −34.359 1.00 26.07ATOM 529 O THR A 69 −26.619 5.905 −34.523 1.00 25.25 ATOM 530 N TYR A 70−27.790 4.064 −35.123 1.00 25.65 ATOM 531 CA TYR A 70 −26.948 3.738−36.267 1.00 25.36 ATOM 532 CB TYR A 70 −27.480 2.504 −37.013 1.00 25.26ATOM 533 CG TYR A 70 −26.638 2.104 −38.217 1.00 25.62 ATOM 534 CD1 TYR A70 −26.949 2.567 −39.498 1.00 25.62 ATOM 535 CE1 TYR A 70 −26.190 2.201−40.611 1.00 26.48 ATOM 536 CZ TYR A 70 −25.099 1.360 −40.437 1.00 25.36ATOM 537 OH TYR A 70 −24.354 0.995 −41.520 1.00 24.80 ATOM 538 CE2 TYR A70 −24.770 0.883 −39.175 1.00 25.59 ATOM 539 CD2 TYR A 70 −25.538 1.259−38.071 1.00 25.36 ATOM 540 C TYR A 70 −26.816 4.909 −37.230 1.00 25.38ATOM 541 O TYR A 70 −27.802 5.573 −37.583 1.00 24.87 ATOM 542 N ASP A 71−25.575 5.127 −37.666 1.00 25.16 ATOM 543 CA ASP A 71 −25.188 6.210−38.550 1.00 25.40 ATOM 544 CB ASP A 71 −24.668 7.404 −37.724 1.00 25.60ATOM 545 CG ASP A 71 −24.361 8.642 −38.573 1.00 26.17 ATOM 546 OD1 ASP A71 −23.801 8.526 −39.681 1.00 25.82 ATOM 547 OD2 ASP A 71 −24.675 9.755−38.108 1.00 27.85 ATOM 548 C ASP A 71 −24.061 5.619 −39.386 1.00 25.64ATOM 549 O ASP A 71 −22.956 5.377 −38.875 1.00 24.82 ATOM 550 N ALA A 72−24.347 5.379 −40.665 1.00 24.95 ATOM 551 CA ALA A 72 −23.380 4.764−41.586 1.00 24.24 ATOM 552 CB ALA A 72 −24.047 4.434 −42.921 1.00 24.35ATOM 553 C ALA A 72 −22.152 5.657 −41.812 1.00 24.04 ATOM 554 O ALA A 72−21.054 5.159 −42.086 1.00 23.21 ATOM 555 N GLY A 73 −22.356 6.970−41.695 1.00 23.63 ATOM 556 CA GLY A 73 −21.265 7.938 −41.761 1.00 24.20ATOM 557 C GLY A 73 −20.285 7.809 −40.596 1.00 23.85 ATOM 558 O GLY A 73−19.067 7.927 −40.806 1.00 24.81 ATOM 559 N LEU A 74 −20.798 7.588−39.376 1.00 22.78 ATOM 560 CA LEU A 74 −19.927 7.347 −38.232 1.00 22.21ATOM 561 CB LEU A 74 −20.662 7.449 −36.879 1.00 22.58 ATOM 562 CG LEU A74 −21.132 8.846 −36.434 1.00 24.06 ATOM 563 CD1 LEU A 74 −21.732 8.793−35.019 1.00 22.31 ATOM 564 CD2 LEU A 74 −20.002 9.869 −36.503 1.0026.04 ATOM 565 C LEU A 74 −19.256 5.999 −38.370 1.00 21.94 ATOM 566 OLEU A 74 −18.060 5.872 −38.098 1.00 20.62 ATOM 567 N GLN A 75 −20.0194.988 −38.814 1.00 21.47 ATOM 568 CA GLN A 75 −19.451 3.654 −38.989 1.0021.07 ATOM 569 CB GLN A 75 −20.469 2.709 −39.619 1.00 21.44 ATOM 570 CGGLN A 75 −20.002 1.280 −39.594 1.00 23.11 ATOM 571 CD GLN A 75 −21.1010.312 −39.945 1.00 24.74 ATOM 572 OE1 GLN A 75 −21.273 −0.719 −39.2901.00 26.57 ATOM 573 NE2 GLN A 75 −21.872 0.654 −40.950 1.00 23.71 ATOM574 C GLN A 75 −18.219 3.704 −39.889 1.00 21.05 ATOM 575 O GLN A 75−17.229 3.046 −39.611 1.00 21.10 ATOM 576 N ARG A 76 −18.294 4.466−40.975 1.00 20.73 ATOM 577 CA ARG A 76 −17.184 4.551 −41.910 1.00 21.56ATOM 578 CB ARG A 76 −17.544 5.460 −43.101 1.00 22.06 ATOM 579 CG ARG A76 −16.452 5.627 −44.168 1.00 24.00 ATOM 580 CD ARG A 76 −15.586 6.895−43.934 1.00 27.60 ATOM 581 NE ARG A 76 −16.275 8.150 −44.280 1.00 30.93ATOM 582 CZ ARG A 76 −15.778 9.378 −44.082 1.00 32.20 ATOM 583 NH1 ARG A76 −14.572 9.556 −43.535 1.00 30.72 ATOM 584 NH2 ARG A 76 −16.491 10.443−44.437 1.00 32.29 ATOM 585 C ARG A 76 −15.942 5.063 −41.162 1.00 20.85ATOM 586 O ARG A 76 −14.858 4.514 −41.296 1.00 20.93 ATOM 587 N ARG A 77−16.116 6.119 −40.378 1.00 20.17 ATOM 588 CA ARG A 77 −14.990 6.723−39.631 1.00 19.61 ATOM 589 CB ARG A 77 −15.419 8.058 −39.009 1.00 19.11ATOM 590 CG ARG A 77 −15.719 9.106 −40.075 1.00 20.18 ATOM 591 CD ARG A77 −16.379 10.299 −39.459 1.00 22.42 ATOM 592 NE ARG A 77 −16.489 11.411−40.396 1.00 24.06 ATOM 593 CZ ARG A 77 −17.501 11.592 −41.243 1.0027.81 ATOM 594 NH1 ARG A 77 −18.508 10.714 −41.303 1.00 28.01 ATOM 595NH2 ARG A 77 −17.509 12.658 −42.033 1.00 27.19 ATOM 596 C ARG A 77−14.425 5.789 −38.570 1.00 18.77 ATOM 597 O ARG A 77 −13.197 5.685−38.411 1.00 18.64 ATOM 598 N ILE A 78 −15.320 5.117 −37.852 1.00 17.79ATOM 599 CA ILE A 78 −14.931 4.125 −36.857 1.00 18.13 ATOM 600 CB ILE A78 −16.165 3.514 −36.151 1.00 17.88 ATOM 601 CG1 ILE A 78 −16.862 4.564−35.282 1.00 18.78 ATOM 602 CD1 ILE A 78 −18.274 4.154 −34.879 1.0019.16 ATOM 603 CG2 ILE A 78 −15.772 2.279 −35.308 1.00 18.15 ATOM 604 CILE A 78 −14.105 3.012 −37.491 1.00 18.09 ATOM 605 O ILE A 78 −13.0882.612 −36.949 1.00 17.42 ATOM 606 N GLU A 79 −14.565 2.495 −38.631 1.0018.82 ATOM 607 CA GLU A 79 −13.826 1.446 −39.341 1.00 20.22 ATOM 608 CBGLU A 79 −14.587 1.017 −40.609 1.00 20.36 ATOM 609 CG GLU A 79 −15.8110.136 −40.312 1.00 22.29 ATOM 610 CD GLU A 79 −16.633 −0.206 −41.5651.00 22.92 ATOM 611 OE1 GLU A 79 −16.345 0.328 −42.670 1.00 26.99 ATOM612 OE2 GLU A 79 −17.579 −1.012 −41.425 1.00 25.69 ATOM 613 C GLU A 79−12.418 1.918 −39.704 1.00 18.80 ATOM 614 O GLU A 79 −11.450 1.191−39.507 1.00 19.44 ATOM 615 N GLN A 80 −12.301 3.147 −40.211 1.00 18.84ATOM 616 CA GLN A 80 −10.998 3.661 −40.636 1.00 17.90 ATOM 617 CB GLN A80 −11.149 4.921 −41.482 1.00 18.92 ATOM 618 CG GLN A 80 −11.794 4.593−42.844 1.00 21.99 ATOM 619 CD GLN A 80 −12.040 5.799 −43.707 1.00 27.48ATOM 620 OE1 GLN A 80 −12.265 6.898 −43.223 1.00 30.45 ATOM 621 NE2 GLNA 80 −12.037 5.586 −45.013 1.00 32.63 ATOM 622 C GLN A 80 −10.059 3.892−39.456 1.00 17.64 ATOM 623 O GLN A 80 −8.862 3.612 −39.535 1.00 17.21ATOM 624 N TYR A 81 −10.607 4.408 −38.365 1.00 17.29 ATOM 625 CA TYR A81 −9.839 4.552 −37.122 1.00 17.64 ATOM 626 CB TYR A 81 −10.750 5.139−36.023 1.00 17.24 ATOM 627 CG TYR A 81 −10.188 4.973 −34.621 1.00 17.79ATOM 628 CD1 TYR A 81 −9.085 5.728 −34.184 1.00 16.36 ATOM 629 CE1 TYR A81 −8.561 5.568 −32.882 1.00 17.45 ATOM 630 CZ TYR A 81 −9.146 4.646−32.009 1.00 16.35 ATOM 631 OH TYR A 81 −8.654 4.457 −30.724 1.00 17.06ATOM 632 CE2 TYR A 81 −10.238 3.890 −32.423 1.00 17.51 ATOM 633 CD2 TYRA 81 −10.754 4.055 −33.729 1.00 17.00 ATOM 634 C TYR A 81 −9.271 3.197−36.686 1.00 18.04 ATOM 635 O TYR A 81 −8.098 3.083 −36.321 1.00 17.85ATOM 636 N ILE A 82 −10.096 2.159 −36.746 1.00 17.99 ATOM 637 CA ILE A82 −9.661 0.839 −36.295 1.00 19.35 ATOM 638 CB ILE A 82 −10.844 −0.166−36.187 1.00 18.93 ATOM 639 CG1 ILE A 82 −11.753 0.233 −35.017 1.0019.40 ATOM 640 CD1 ILE A 82 −13.093 −0.565 −34.896 1.00 20.46 ATOM 641CG2 ILE A 82 −10.301 −1.587 −35.984 1.00 20.61 ATOM 642 C ILE A 82−8.547 0.292 −37.194 1.00 19.92 ATOM 643 O ILE A 82 −7.543 −0.239−36.708 1.00 20.26 ATOM 644 N THR A 83 −8.713 0.432 −38.503 1.00 20.05ATOM 645 CA THR A 83 −7.709 −0.100 −39.406 1.00 21.11 ATOM 646 CB THR A83 −8.241 −0.297 −40.845 1.00 21.63 ATOM 647 OG1 THR A 83 −8.830 0.902−41.306 1.00 25.88 ATOM 648 CG2 THR A 83 −9.330 −1.347 −40.851 1.0021.56 ATOM 649 C THR A 83 −6.410 0.690 −39.337 1.00 20.59 ATOM 650 O THRA 83 −5.338 0.105 −39.511 1.00 20.72 ATOM 651 N ALA A 84 −6.494 1.997−39.050 1.00 19.51 ATOM 652 CA ALA A 84 −5.292 2.809 −38.777 1.00 19.37ATOM 653 CB ALA A 84 −5.652 4.290 −38.507 1.00 19.42 ATOM 654 C ALA A 84−4.436 2.231 −37.643 1.00 19.32 ATOM 655 O ALA A 84 −3.208 2.370 −37.6491.00 19.47 ATOM 656 N GLN A 85 −5.063 1.535 −36.695 1.00 19.34 ATOM 657CA GLN A 85 −4.325 0.998 −35.544 1.00 18.78 ATOM 658 CB GLN A 85 −5.2660.609 −34.396 1.00 19.29 ATOM 659 CG GLN A 85 −6.260 1.735 −34.007 1.0017.98 ATOM 660 CD GLN A 85 −5.593 3.098 −33.830 1.00 17.20 ATOM 661 OE1GLN A 85 −6.021 4.095 −34.418 1.00 20.82 ATOM 662 NE2 GLN A 85 −4.5403.143 −33.034 1.00 13.47 ATOM 663 C GLN A 85 −3.447 −0.178 −35.932 1.0019.08 ATOM 664 O GLN A 85 −2.478 −0.473 −35.251 1.00 17.94 ATOM 665 NVAL A 86 −3.808 −0.838 −37.032 1.00 19.32 ATOM 666 CA VAL A 86 −2.999−1.928 −37.588 1.00 20.79 ATOM 667 CB VAL A 86 −3.670 −2.581 −38.8231.00 21.18 ATOM 668 CG1 VAL A 86 −2.712 −3.615 −39.454 1.00 22.66 ATOM669 CG2 VAL A 86 −4.980 −3.250 −38.400 1.00 21.47 ATOM 670 C VAL A 86−1.617 −1.381 −37.940 1.00 20.63 ATOM 671 O VAL A 86 −0.602 −1.930−37.520 1.00 21.41 ATOM 672 N THR A 87 −1.604 −0.251 −38.641 1.00 20.67ATOM 673 CA THR A 87 −0.361 0.419 −39.015 1.00 21.10 ATOM 674 CB THR A87 −0.659 1.583 −39.986 1.00 21.59 ATOM 675 OG1 THR A 87 −1.176 1.033−41.202 1.00 23.63 ATOM 676 CG2 THR A 87 0.585 2.370 −40.305 1.00 22.02ATOM 677 C THR A 87 0.412 0.881 −37.795 1.00 20.28 ATOM 678 O THR A 871.620 0.641 −37.679 1.00 20.22 ATOM 679 N LEU A 88 −0.280 1.543 −36.8741.00 19.11 ATOM 680 CA LEU A 88 0.367 2.097 −35.697 1.00 18.71 ATOM 681CB LEU A 88 −0.585 3.015 −34.903 1.00 18.08 ATOM 682 CG LEU A 88 −1.0164.294 −35.596 1.00 18.50 ATOM 683 CD1 LEU A 88 −2.038 5.058 −34.706 1.0019.12 ATOM 684 CD2 LEU A 88 0.206 5.193 −35.937 1.00 19.81 ATOM 685 CLEU A 88 0.976 1.057 −34.780 1.00 18.33 ATOM 686 O LEU A 88 2.101 1.244−34.336 1.00 18.76 ATOM 687 N GLN A 89 0.255 −0.029 −34.492 1.00 18.75ATOM 688 CA GLN A 89 0.809 −1.085 −33.623 1.00 19.67 ATOM 689 CB GLN A89 −0.199 −2.201 −33.373 1.00 19.69 ATOM 690 CG GLN A 89 −1.397 −1.775−32.564 1.00 19.25 ATOM 691 CD GLN A 89 −2.140 −2.951 −32.004 1.00 20.83ATOM 692 OE1 GLN A 89 −2.121 −4.037 −32.580 1.00 19.26 ATOM 693 NE2 GLNA 89 −2.802 −2.751 −30.861 1.00 19.61 ATOM 694 C GLN A 89 2.097 −1.683−34.203 1.00 20.68 ATOM 695 O GLN A 89 3.013 −2.026 −33.461 1.00 21.21ATOM 696 N GLY A 90 2.164 −1.778 −35.524 1.00 21.75 ATOM 697 CA GLY A 903.330 −2.374 −36.173 1.00 23.35 ATOM 698 C GLY A 90 4.604 −1.552 −36.0961.00 24.79 ATOM 699 O GLY A 90 5.699 −2.104 −36.299 1.00 25.52 ATOM 700N ASN A 91 4.477 −0.252 −35.796 1.00 25.17 ATOM 701 CA ASN A 91 5.5960.714 −35.870 1.00 26.14 ATOM 702 CB ASN A 91 5.108 2.161 −35.653 1.0026.83 ATOM 703 CG ASN A 91 4.615 2.849 −36.919 1.00 29.67 ATOM 704 OD1ASN A 91 4.869 2.414 −38.051 1.00 34.53 ATOM 705 ND2 ASN A 91 3.9273.981 −36.724 1.00 32.76 ATOM 706 C ASN A 91 6.656 0.489 −34.820 1.0025.67 ATOM 707 O ASN A 91 6.346 0.385 −33.644 1.00 25.70 ATOM 708 N SERA 92 7.918 0.472 −35.227 1.00 25.32 ATOM 709 CA SER A 92 8.990 0.668−34.257 1.00 25.27 ATOM 710 CB SER A 92 10.314 0.107 −34.775 1.00 26.03ATOM 711 OG SER A 92 10.212 −1.305 −34.803 1.00 30.67 ATOM 712 C SER A92 9.103 2.171 −34.003 1.00 23.80 ATOM 713 O SER A 92 9.055 2.979−34.942 1.00 24.56 ATOM 714 N ASN A 93 9.246 2.544 −32.743 1.00 22.30ATOM 715 CA ASN A 93 9.236 3.953 −32.383 1.00 21.23 ATOM 716 CB ASN A 937.769 4.423 −32.201 1.00 21.41 ATOM 717 CG ASN A 93 7.075 3.704 −31.0511.00 19.23 ATOM 718 OD1 ASN A 93 7.564 3.736 −29.927 1.00 17.81 ATOM 719ND2 ASN A 93 5.974 3.024 −31.335 1.00 19.43 ATOM 720 C ASN A 93 10.1034.149 −31.150 1.00 20.39 ATOM 721 O ASN A 93 10.625 3.154 −30.607 1.0019.46 ATOM 722 N PRO A 94 10.337 5.410 −30.732 1.00 19.95 ATOM 723 CAPRO A 94 11.228 5.604 −29.574 1.00 19.89 ATOM 724 CB PRO A 94 11.2357.131 −29.385 1.00 19.51 ATOM 725 CG PRO A 94 10.988 7.653 −30.753 1.0019.96 ATOM 726 CD PRO A 94 9.952 6.717 −31.325 1.00 19.99 ATOM 727 C PROA 94 10.870 4.898 −28.263 1.00 20.64 ATOM 728 O PRO A 94 11.756 4.727−27.430 1.00 20.54 ATOM 729 N SER A 95 9.610 4.485 −28.073 1.00 20.36ATOM 730 CA SER A 95 9.264 3.674 −26.902 1.00 21.00 ATOM 731 CB SER A 957.770 3.736 −26.587 1.00 20.05 ATOM 732 OG SER A 95 7.413 5.036 −26.1471.00 19.97 ATOM 733 C SER A 95 9.679 2.204 −27.066 1.00 21.73 ATOM 734 OSER A 95 9.809 1.499 −26.072 1.00 22.10 ATOM 735 N GLY A 96 9.853 1.748−28.306 1.00 21.90 ATOM 736 CA GLY A 96 10.229 0.350 −28.562 1.00 23.56ATOM 737 C GLY A 96 9.506 −0.196 −29.774 1.00 24.14 ATOM 738 O GLY A 969.121 0.557 −30.664 1.00 24.24 ATOM 739 N SER A 97 9.315 −1.510 −29.8281.00 25.24 ATOM 740 CA SER A 97 8.703 −2.116 −31.000 1.00 25.77 ATOM 741CB SER A 97 9.751 −2.874 −31.834 1.00 27.15 ATOM 742 OG SER A 97 10.120−4.086 −31.189 1.00 30.57 ATOM 743 C SER A 97 7.590 −3.042 −30.571 1.0025.27 ATOM 744 O SER A 97 7.346 −3.199 −29.376 1.00 24.85 ATOM 745 N LEUA 98 6.930 −3.655 −31.543 1.00 24.82 ATOM 746 CA LEU A 98 5.826 −4.559−31.252 1.00 25.88 ATOM 747 CB LEU A 98 4.982 −4.813 −32.504 1.00 25.31ATOM 748 CG LEU A 98 3.714 −5.673 −32.420 1.00 25.89 ATOM 749 CD1 LEU A98 2.745 −5.169 −31.337 1.00 25.58 ATOM 750 CD2 LEU A 98 3.006 −5.724−33.778 1.00 26.27 ATOM 751 C LEU A 98 6.310 −5.866 −30.604 1.00 26.75ATOM 752 O LEU A 98 5.607 −6.438 −29.762 1.00 27.41 ATOM 753 N ALA A 997.528 −6.290 −30.950 1.00 27.23 ATOM 754 CA ALA A 99 8.074 −7.590−30.533 1.00 27.89 ATOM 755 CB ALA A 99 9.566 −7.700 −30.935 1.00 27.68ATOM 756 C ALA A 99 7.893 −7.911 −29.053 1.00 27.86 ATOM 757 O ALA A 997.450 −9.007 −28.711 1.00 28.77 ATOM 758 N ASP A 100 8.241 −6.966−28.181 1.00 27.75 ATOM 759 CA ASP A 100 8.030 −7.137 −26.741 1.00 27.20ATOM 760 CB ASP A 100 9.328 −6.937 −25.966 1.00 27.10 ATOM 761 CG ASP A100 9.845 −5.525 −26.038 1.00 30.19 ATOM 762 OD1 ASP A 100 10.891 −5.281−25.419 1.00 32.28 ATOM 763 OD2 ASP A 100 9.225 −4.654 −26.694 1.0030.36 ATOM 764 C ASP A 100 6.905 −6.256 −26.173 1.00 25.74 ATOM 765 OASP A 100 6.761 −6.108 −24.956 1.00 26.33 ATOM 766 N GLY A 101 6.118−5.683 −27.075 1.00 24.93 ATOM 767 CA GLY A 101 4.982 −4.853 −26.7071.00 23.22 ATOM 768 C GLY A 101 5.326 −3.418 −26.342 1.00 22.68 ATOM 769O GLY A 101 4.419 −2.580 −26.287 1.00 21.48 ATOM 770 N SER A 102 6.609−3.117 −26.126 1.00 21.53 ATOM 771 CA SER A 102 6.996 −1.815 −25.5631.00 21.49 ATOM 772 CB SER A 102 8.483 −1.739 −25.199 1.00 22.07 ATOM773 OG SER A 102 9.283 −1.958 −26.345 1.00 21.77 ATOM 774 C SER A 1026.604 −0.643 −26.449 1.00 20.66 ATOM 775 O SER A 102 6.279 0.403 −25.9251.00 20.67 ATOM 776 N GLY A 103 6.636 −0.819 −27.771 1.00 19.97 ATOM 777CA GLY A 103 6.257 0.255 −28.707 1.00 19.46 ATOM 778 C GLY A 103 4.8240.777 −28.539 1.00 18.94 ATOM 779 O GLY A 103 4.525 1.903 −28.945 1.0018.13 ATOM 780 N LEU A 104 3.939 −0.043 −27.956 1.00 18.13 ATOM 781 CALEU A 104 2.517 0.326 −27.818 1.00 16.92 ATOM 782 CB LEU A 104 1.672−0.924 −27.447 1.00 17.28 ATOM 783 CG LEU A 104 1.715 −2.104 −28.4301.00 16.76 ATOM 784 CD1 LEU A 104 1.072 −3.356 −27.836 1.00 21.62 ATOM785 CD2 LEU A 104 1.069 −1.751 −29.761 1.00 19.06 ATOM 786 C LEU A 1042.283 1.464 −26.798 1.00 16.57 ATOM 787 O LEU A 104 1.202 2.092 −26.8071.00 16.79 ATOM 788 N GLY A 105 3.279 1.713 −25.936 1.00 14.86 ATOM 789CA GLY A 105 3.255 2.802 −24.938 1.00 15.94 ATOM 790 C GLY A 105 3.5584.199 −25.482 1.00 15.05 ATOM 791 O GLY A 105 3.481 5.179 −24.755 1.0015.93 ATOM 792 N GLU A 106 3.869 4.292 −26.780 1.00 14.63 ATOM 793 CAGLU A 106 4.236 5.548 −27.416 1.00 14.49 ATOM 794 CB GLU A 106 4.7285.250 −28.847 1.00 13.83 ATOM 795 CG GLU A 106 5.215 6.470 −29.678 1.0016.14 ATOM 796 CD GLU A 106 6.479 7.155 −29.139 1.00 18.44 ATOM 797 OE1GLU A 106 6.978 6.817 −28.044 1.00 21.44 ATOM 798 OE2 GLU A 106 6.9728.083 −29.817 1.00 21.04 ATOM 799 C GLU A 106 3.012 6.484 −27.413 1.0014.32 ATOM 800 O GLU A 106 1.928 6.074 −27.828 1.00 15.51 ATOM 801 N PROA 107 3.164 7.706 −26.890 1.00 15.21 ATOM 802 CA PRO A 107 2.025 8.645−26.772 1.00 14.90 ATOM 803 CB PRO A 107 2.598 9.809 −25.951 1.00 15.27ATOM 804 CG PRO A 107 3.833 9.290 −25.310 1.00 17.25 ATOM 805 CD PRO A107 4.385 8.238 −26.243 1.00 14.35 ATOM 806 C PRO A 107 1.468 9.219−28.066 1.00 14.48 ATOM 807 O PRO A 107 0.263 9.371 −28.172 1.00 13.94ATOM 808 N LYS A 108 2.320 9.567 −29.027 1.00 14.24 ATOM 809 CA LYS A108 1.837 10.309 −30.204 1.00 14.51 ATOM 810 CB LYS A 108 1.853 11.828−29.960 1.00 14.26 ATOM 811 CG LYS A 108 3.225 12.524 −30.029 1.00 13.88ATOM 812 CD LYS A 108 3.102 14.033 −29.775 1.00 15.15 ATOM 813 CB LYS A108 4.299 14.820 −30.283 1.00 17.08 ATOM 814 NZ LYS A 108 4.341 16.279−29.836 1.00 15.57 ATOM 815 C LYS A 108 2.608 9.953 −31.454 1.00 14.69ATOM 816 O LYS A 108 3.734 9.442 −31.377 1.00 14.67 ATOM 817 N PHE A 1091.976 10.203 −32.594 1.00 14.54 ATOM 818 CA PHE A 109 2.530 9.860−33.902 1.00 15.20 ATOM 819 CB PHE A 109 1.839 8.594 −34.451 1.00 15.67ATOM 820 CG PHE A 109 1.973 7.407 −33.553 1.00 16.81 ATOM 821 CD1 PHE A109 1.081 7.219 −32.490 1.00 17.93 ATOM 822 CE1 PHE A 109 1.205 6.117−31.649 1.00 21.93 ATOM 823 CZ PHE A 109 2.241 5.210 −31.834 1.00 19.06ATOM 824 CE2 PHE A 109 3.141 5.384 −32.883 1.00 20.27 ATOM 825 CD2 PHE A109 3.003 6.492 −33.737 1.00 19.44 ATOM 826 C PHE A 109 2.301 10.992−34.881 1.00 15.19 ATOM 827 O PHE A 109 1.450 11.861 −34.655 1.00 14.41ATOM 828 N GLU A 110 3.039 10.971 −35.993 1.00 15.14 ATOM 829 CA GLU A110 2.756 11.905 −37.077 1.00 15.24 ATOM 830 CB GLU A 110 3.905 11.933−38.103 1.00 15.00 ATOM 831 CG GLU A 110 5.302 12.204 −37.493 1.00 16.29ATOM 832 CD GLU A 110 5.554 13.673 −37.174 1.00 17.52 ATOM 833 OE1 GLU A110 4.708 14.544 −37.504 1.00 17.65 ATOM 834 OE2 GLU A 110 6.619 13.963−36.587 1.00 18.74 ATOM 835 C GLU A 110 1.462 11.476 −37.762 1.00 15.32ATOM 836 O GLU A 110 1.093 10.278 −37.753 1.00 15.26 ATOM 837 N LEU A111 0.776 12.445 −38.360 1.00 15.59 ATOM 838 CA LEU A 111 −0.522 12.186−39.009 1.00 16.33 ATOM 839 CB LEU A 111 −1.265 13.510 −39.163 1.0016.57 ATOM 840 CG LEU A 111 −1.770 13.908 −37.756 1.00 18.11 ATOM 841CD1 LEU A 111 −1.819 15.405 −37.574 1.00 21.43 ATOM 842 CD2 LEU A 111−3.151 13.204 −37.506 1.00 18.74 ATOM 843 C LEU A 111 −0.409 11.436−40.350 1.00 17.37 ATOM 844 O LEU A 111 −1.426 11.023 −40.944 1.00 17.23ATOM 845 N THR A 112 0.833 11.258 −40.815 1.00 17.42 ATOM 846 CA THR A112 1.144 10.301 −41.887 1.00 17.92 ATOM 847 CB THR A 112 2.512 10.619−42.499 1.00 17.98 ATOM 848 OG1 THR A 112 3.476 10.702 −41.445 1.0018.32 ATOM 849 CG2 THR A 112 2.486 11.945 −43.228 1.00 19.47 ATOM 850 CTHR A 112 1.215 8.846 −41.356 1.00 18.90 ATOM 851 O THR A 112 1.5357.917 −42.117 1.00 17.68 ATOM 852 N LEU A 113 0.944 8.664 −40.055 1.0018.48 ATOM 853 CA LEU A 113 1.041 7.379 −39.348 1.00 19.78 ATOM 854 CBLEU A 113 0.061 6.319 −39.904 1.00 19.45 ATOM 855 CG LEU A 113 −1.4116.699 −40.074 1.00 21.71 ATOM 856 CD1 LEU A 113 −2.194 5.470 −40.4771.00 23.46 ATOM 857 CD2 LEU A 113 −2.005 7.323 −38.800 1.00 21.59 ATOM858 C LEU A 113 2.481 6.866 −39.338 1.00 20.43 ATOM 859 O LEU A 1132.737 5.704 −39.653 1.00 20.96 ATOM 860 N LYS A 114 3.406 7.769 −39.0241.00 20.07 ATOM 861 CA LYS A 114 4.826 7.460 −38.863 1.00 20.25 ATOM 862CB LYS A 114 5.662 8.209 −39.899 1.00 20.95 ATOM 863 CG LYS A 114 5.4327.725 −41.314 1.00 25.23 ATOM 864 CD LYS A 114 6.636 8.059 −42.184 1.0033.76 ATOM 865 CE LYS A 114 6.551 7.360 −43.537 1.00 38.31 ATOM 866 NZLYS A 114 5.285 7.711 −44.251 1.00 41.29 ATOM 867 C LYS A 114 5.2527.874 −37.471 1.00 19.64 ATOM 868 O LYS A 114 4.576 8.708 −36.845 1.0019.39 ATOM 869 N PRO A 115 6.376 7.318 −36.973 1.00 19.06 ATOM 870 CAPRO A 115 6.750 7.626 −35.601 1.00 18.72 ATOM 871 CB PRO A 115 7.9636.712 −35.326 1.00 19.82 ATOM 872 CG PRO A 115 8.101 5.814 −36.500 1.0020.93 ATOM 873 CD PRO A 115 7.339 6.412 −37.639 1.00 19.08 ATOM 874 CPRO A 115 7.156 9.093 −35.434 1.00 18.70 ATOM 875 O PRO A 115 7.6949.724 −36.375 1.00 17.25 ATOM 876 N PHE A 116 6.844 9.628 −34.256 1.0018.55 ATOM 877 CA PHE A 116 7.342 10.918 −33.805 1.00 18.27 ATOM 878 CBPHE A 116 6.359 11.566 −32.809 1.00 18.41 ATOM 879 CG PHE A 116 6.90812.804 −32.151 1.00 17.33 ATOM 880 CD1 PHE A 116 6.942 14.014 −32.8471.00 16.98 ATOM 881 CE1 PHE A 116 7.457 15.173 −32.254 1.00 16.22 ATOM882 CZ PHE A 116 7.950 15.138 −30.935 1.00 15.88 ATOM 883 CE2 PHE A 1167.902 13.917 −30.216 1.00 16.74 ATOM 884 CD2 PHE A 116 7.380 12.767−30.825 1.00 16.05 ATOM 885 C PHE A 116 8.701 10.695 −33.141 1.00 19.14ATOM 886 O PHE A 116 8.808 9.987 −32.134 1.00 19.66 ATOM 887 N THR A 1179.746 11.299 −33.713 1.00 19.53 ATOM 888 CA THR A 117 11.116 11.020−33.315 1.00 20.15 ATOM 889 CB THR A 117 12.042 10.999 −34.567 1.0020.83 ATOM 890 OG1 THR A 117 11.988 12.277 −35.222 1.00 22.59 ATOM 891CG2 THR A 117 11.576 9.895 −35.557 1.00 21.40 ATOM 892 C THR A 11711.685 11.969 −32.263 1.00 20.34 ATOM 893 O THR A 117 12.813 11.768−31.774 1.00 21.13 ATOM 894 N GLY A 118 10.943 13.017 −31.914 1.00 19.25ATOM 895 CA GLY A 118 11.451 14.018 −30.974 1.00 19.41 ATOM 896 C GLY A118 11.431 13.498 −29.541 1.00 19.75 ATOM 897 O GLY A 118 10.913 12.397−29.281 1.00 19.99 ATOM 898 N ASN A 119 11.998 14.279 −28.622 1.00 19.56ATOM 899 CA ASN A 119 11.958 13.954 −27.198 1.00 20.41 ATOM 900 CB ASN A119 12.961 14.801 −26.419 1.00 21.50 ATOM 901 CG ASN A 119 14.377 14.612−26.930 1.00 25.14 ATOM 902 OD1 ASN A 119 14.779 13.500 −27.294 1.0030.77 ATOM 903 ND2 ASN A 119 15.131 15.693 −26.987 1.00 31.23 ATOM 904 CASN A 119 10.550 14.194 −26.696 1.00 20.06 ATOM 905 O ASN A 119 9.88115.089 −27.167 1.00 19.00 ATOM 906 N TRP A 120 10.084 13.348 −25.7871.00 19.74 ATOM 907 CA TRP A 120 8.707 13.466 −25.316 1.00 19.03 ATOM908 CB TRP A 120 7.717 12.917 −26.359 1.00 18.71 ATOM 909 CG TRP A 1206.351 13.522 −26.162 1.00 19.76 ATOM 910 CD1 TRP A 120 5.239 12.901−25.673 1.00 19.81 ATOM 911 NE1 TRP A 120 4.186 13.799 −25.593 1.0019.49 ATOM 912 CE2 TRP A 120 4.612 15.021 −26.042 1.00 19.44 ATOM 913CD2 TRP A 120 5.975 14.886 −26.410 1.00 19.35 ATOM 914 CE3 TRP A 1206.657 16.014 −26.895 1.00 18.94 ATOM 915 CZ3 TRP A 120 5.959 17.220−27.010 1.00 20.22 ATOM 916 CH2 TRP A 120 4.602 17.315 −26.628 1.0020.15 ATOM 917 CZ2 TRP A 120 3.918 16.233 −26.160 1.00 18.83 ATOM 918 CTRP A 120 8.602 12.685 −24.001 1.00 18.80 ATOM 919 O TRP A 120 9.45411.833 −23.722 1.00 18.83 ATOM 920 N GLY A 121 7.593 12.990 −23.189 1.0017.91 ATOM 921 CA GLY A 121 7.314 12.189 −21.988 1.00 17.64 ATOM 922 CGLY A 121 6.721 10.834 −22.362 1.00 18.93 ATOM 923 O GLY A 121 5.49910.704 −22.487 1.00 18.99 ATOM 924 N ARG A 122 7.589 9.828 −22.536 1.0017.95 ATOM 925 CA ARG A 122 7.195 13.483 −22.958 1.00 17.86 ATOM 926 CBARG A 122 7.686 8.193 −24.394 1.00 17.37 ATOM 927 CG ARG A 122 9.1818.529 −24.626 1.00 19.53 ATOM 928 CD ARG A 122 9.689 7.987 −25.969 1.0017.88 ATOM 929 NE ARG A 122 9.012 8.549 −27.159 1.00 18.08 ATOM 930 CZARG A 122 9.425 9.645 −27.807 1.00 18.06 ATOM 931 NH1 ARG A 122 10.47710.326 −27.366 1.00 16.88 ATOM 932 NH2 ARG A 122 8.784 10.074 −28.8921.00 17.35 ATOM 933 C ARG A 122 7.799 7.450 −21.976 1.00 17.48 ATOM 934O ARG A 122 8.848 7.697 −21.396 1.00 17.69 ATOM 935 N PRO A 123 7.1426.298 −21.781 1.00 17.14 ATOM 936 CA PRO A 123 5.886 5.916 −22.382 1.0016.01 ATOM 937 CB PRO A 123 5.908 4.385 −22.266 1.00 16.51 ATOM 938 CGPRO A 123 6.585 4.144 −20.969 1.00 16.30 ATOM 939 CD PRO A 123 7.6585.238 −20.873 1.00 16.95 ATOM 940 C PRO A 123 4.716 6.494 −21.581 1.0015.29 ATOM 941 O PRO A 123 4.926 7.057 −20.521 1.00 15.07 ATOM 942 N GLNA 124 3.504 6.362 −22.120 1.00 14.60 ATOM 943 CA GLN A 124 2.289 6.675−21.386 1.00 14.40 ATOM 944 CB GLN A 124 1.602 7.889 −22.001 1.00 14.71ATOM 945 CG GLN A 124 2.442 9.186 −21.711 1.00 11.93 ATOM 946 CD GLN A124 1.993 10.407 −22.472 1.00 15.67 ATOM 947 OE1 GLN A 124 2.807 11.310−22.758 1.00 15.75 ATOM 948 NE2 GLN A 124 0.718 10.450 −22.822 1.00 9.85ATOM 949 C GLN A 124 1.441 5.421 −21.511 1.00 14.28 ATOM 950 O GLN A 1240.988 5.095 −22.604 1.00 14.63 ATOM 951 N ARG A 125 1.241 4.731 −20.3901.00 13.50 ATOM 952 CA ARG A 125 0.700 3.382 −20.398 1.00 13.96 ATOM 953CB ARG A 125 1.331 2.567 −19.256 1.00 14.28 ATOM 954 CG ARG A 125 2.8642.703 −19.249 1.00 15.16 ATOM 955 CD ARG A 125 3.503 1.577 −18.439 1.0018.07 ATOM 956 NE ARG A 125 4.924 1.827 −18.132 1.00 17.46 ATOM 957 CZARG A 125 5.944 1.334 −18.833 1.00 19.43 ATOM 958 NH1 ARG A 125 5.7280.601 −19.925 1.00 20.02 ATOM 959 NH2 ARG A 125 7.197 1.596 −18.453 1.0018.94 ATOM 960 C ARG A 125 −0.829 3.335 −20.359 1.00 14.48 ATOM 961 OARG A 125 −1.424 2.262 −20.343 1.00 14.40 ATOM 962 N ASP A 126 −1.4624.509 −20.374 1.00 14.03 ATOM 963 CA ASP A 126 −2.919 4.568 −20.542 1.0013.39 ATOM 964 CB ASP A 126 −3.488 5.922 −20.067 1.00 13.17 ATOM 965 CGASP A 126 −2.926 7.092 −20.845 1.00 14.17 ATOM 966 OD1 ASP A 126 −1.7137.108 −21.143 1.00 12.29 ATOM 967 OD2 ASP A 126 −3.705 8.003 −21.1871.00 16.69 ATOM 968 C ASP A 126 −3.350 4.306 −21.974 1.00 13.60 ATOM 969O ASP A 126 −4.452 3.806 −22.189 1.00 13.56 ATOM 970 N GLY A 127 −2.4914.634 −22.948 1.00 12.78 ATOM 971 CA GLY A 127 −2.886 4.558 −24.358 1.0013.20 ATOM 972 C GLY A 127 −3.473 3.213 −24.794 1.00 12.77 ATOM 973 OGLY A 127 −4.579 3.150 −25.327 1.00 12.56 ATOM 974 N PRO A 128 −2.7202.120 −24.613 1.00 13.94 ATOM 975 CA PRO A 128 −3.262 0.810 −24.978 1.0012.97 ATOM 976 CB PRO A 128 −2.135 −0.162 −24.552 1.00 14.15 ATOM 977 CGPRO A 128 −0.907 0.656 −24.721 1.00 14.39 ATOM 978 CD PRO A 128 −1.3232.010 −24.150 1.00 13.67 ATOM 979 C PRO A 128 −4.571 0.455 −24.255 1.0013.30 ATOM 980 O PRO A 128 −5.433 −0.161 −24.869 1.00 13.72 ATOM 981 NALA A 129 −4.718 0.852 −22.985 1.00 12.95 ATOM 982 CA ALA A 129 −5.9630.611 −22.258 1.00 13.49 ATOM 983 CB ALA A 129 −5.806 1.016 −20.808 1.0013.00 ATOM 984 C ALA A 129 −7.162 1.329 −22.923 1.00 13.43 ATOM 985 OALA A 129 −8.217 0.721 −23.159 1.00 13.26 ATOM 986 N LEU A 130 −6.9982.619 −23.221 1.00 12.51 ATOM 987 CA LEU A 130 −8.068 3.409 −23.813 1.0012.69 ATOM 988 CB LEU A 130 −7.678 4.903 −23.806 1.00 12.56 ATOM 989 CGLEU A 130 −7.458 5.555 −22.426 1.00 14.76 ATOM 990 CD1 LEU A 130 −6.9596.991 −22.643 1.00 15.23 ATOM 991 CD2 LEU A 130 −8.776 5.544 −21.6511.00 15.30 ATOM 992 C LEU A 130 −8.410 2.934 −25.228 1.00 12.78 ATOM 993O LEU A 130 −9.571 2.863 −25.607 1.00 12.83 ATOM 994 N ARG A 131 −7.3862.601 −26.015 1.00 13.70 ATOM 995 CA ARG A 131 −7.630 2.070 −27.351 1.0014.52 ATOM 996 CB ARG A 131 −6.316 1.925 −28.135 1.00 14.04 ATOM 997 CGARG A 131 −6.550 1.438 −29.566 1.00 15.60 ATOM 998 CD ARG A 131 −5.2781.522 −30.428 1.00 15.59 ATOM 999 NE ARG A 131 −4.118 0.915 −29.779 1.0016.77 ATOM 1000 CZ ARG A 131 −2.860 1.205 −30.098 1.00 16.26 ATOM 1001NH1 ARG A 131 −2.610 2.104 −31.054 1.00 16.37 ATOM 1002 NH2 ARG A 131−1.856 0.618 −29.448 1.00 15.96 ATOM 1003 C ARG A 131 −8.408 0.729−27.283 1.00 14.44 ATOM 1004 O ARG A 131 −9.350 0.533 −28.050 1.00 15.71ATOM 1005 N ALA A 132 −8.025 −0.164 −26.364 1.00 14.50 ATOM 1006 CA ALAA 132 −8.738 −1.456 −26.195 1.00 15.06 ATOM 1007 CB ALA A 132 −8.069−2.348 −25.112 1.00 15.02 ATOM 1008 C ALA A 132 −10.194 −1.197 −25.8461.00 15.43 ATOM 1009 O ALA A 132 −11.101 −1.808 −26.416 1.00 15.57 ATOM1010 N ILE A 133 −10.418 −0.270 −24.915 1.00 15.70 ATOM 1011 CA ILE A133 −11.777 0.049 −24.491 1.00 14.44 ATOM 1012 CB ILE A 133 −11.7751.056 −23.335 1.00 14.07 ATOM 1013 CG1 ILE A 133 −11.268 0.387 −22.0461.00 15.40 ATOM 1014 CD1 ILE A 133 −10.751 1.388 −21.017 1.00 16.66 ATOM1015 CG2 ILE A 133 −13.176 1.702 −23.101 1.00 13.98 ATOM 1016 C ILE A133 −12.633 0.517 −25.679 1.00 14.36 ATOM 1017 O ILE A 133 −13.781 0.102−25.807 1.00 14.69 ATOM 1018 N ALA A 134 −12.079 1.362 −26.545 1.0013.69 ATOM 1019 CA ALA A 134 −12.819 1.832 −27.720 1.00 13.81 ATOM 1020CB ALA A 134 −12.019 2.949 −28.452 1.00 13.99 ATOM 1021 C ALA A 134−13.140 0.662 −28.657 1.00 14.62 ATOM 1022 O ALA A 134 −14.279 0.473−29.087 1.00 14.90 ATOM 1023 N LEU A 135 −12.133 −0.155 −28.947 1.0014.66 ATOM 1024 CA LEU A 135 −12.328 −1.251 −29.901 1.00 15.75 ATOM 1025CB LEU A 135 −10.984 −1.875 −30.311 1.00 15.75 ATOM 1026 CG LEU A 135−10.348 −1.231 −31.557 1.00 16.40 ATOM 1027 CD1 LEU A 135 −10.257 0.308−31.471 1.00 18.56 ATOM 1028 CD2 LEU A 135 −8.980 −1.852 −31.804 1.0017.85 ATOM 1029 C LEU A 135 −13.277 −2.306 −29.340 1.00 15.13 ATOM 1030O LEU A 135 −14.079 −2.845 −30.087 1.00 15.84 ATOM 1031 N ILE A 136−13.192 −2.573 −28.039 1.00 15.22 ATOM 1032 CA ILE A 136 −14.153 −3.473−27.377 1.00 15.71 ATOM 1033 CB ILE A 136 −13.734 −3.829 −25.918 1.0015.92 ATOM 1034 CG1 ILE A 136 −12.408 −4.598 −25.904 1.00 15.39 ATOM1035 CD1 ILE A 136 −11.742 −4.679 −24.497 1.00 15.63 ATOM 1036 CG2 ILE A136 −14.842 −4.611 −25.204 1.00 16.20 ATOM 1037 C ILE A 136 −15.565−2.902 −27.457 1.00 17.10 ATOM 1038 O ILE A 136 −16.531 −3.631 −27.7281.00 17.48 ATOM 1039 N GLY A 137 −15.685 −1.581 −27.297 1.00 16.46 ATOM1040 CA GLY A 137 −16.979 −0.902 −27.484 1.00 16.59 ATOM 1041 C GLY A137 −17.600 −1.206 −28.833 1.00 17.13 ATOM 1042 O GLY A 137 −18.778−1.605 −28.920 1.00 16.92 ATOM 1043 N TYR A 138 −16.817 −1.056 −29.8981.00 16.61 ATOM 1044 CA TYR A 138 −17.353 −1.349 −31.224 1.00 17.93 ATOM1045 CB TYR A 138 −16.446 −0.838 −32.341 1.00 17.46 ATOM 1046 CG TYR A138 −17.112 −0.897 −33.693 1.00 18.28 ATOM 1047 CD1 TYR A 138 −18.350−0.268 −33.914 1.00 18.85 ATOM 1048 CE1 TYR A 138 −18.966 −0.314 −35.1531.00 21.29 ATOM 1049 CZ TYR A 138 −18.358 −1.001 −36.207 1.00 20.99 ATOM1050 OH TYR A 138 −18.994 −1.055 −37.433 1.00 20.06 ATOM 1051 CE2 TYR A138 −17.133 −1.636 −36.026 1.00 19.88 ATOM 1052 CD2 TYR A 138 −16.512−1.583 −34.766 1.00 18.25 ATOM 1053 C TYR A 138 −17.643 −2.844 −31.4061.00 18.67 ATOM 1054 O TYR A 138 −18.654 −3.207 −32.037 1.00 20.06 ATOM1055 N SER A 139 −16.766 −3.686 −30.864 1.00 19.48 ATOM 1056 CA SER A139 −16.942 −5.146 −30.900 1.00 21.02 ATOM 1057 CB SER A 139 −15.808−5.829 −30.129 1.00 21.09 ATOM 1058 OG SER A 139 −14.581 −5.598 −30.7891.00 21.49 ATOM 1059 C SER A 139 −18.298 −5.557 −30.325 1.00 22.24 ATOM1060 O SER A 139 −19.002 −6.392 −30.907 1.00 23.64 ATOM 1061 N LYS A 140−18.669 −4.976 −29.188 1.00 22.77 ATOM 1062 CA LYS A 140 −19.987 −5.225−28.595 1.00 24.29 ATOM 1063 CB LYS A 140 −20.218 −4.343 −27.370 1.0024.29 ATOM 1064 CG LYS A 140 −19.384 −4.695 −26.170 1.00 26.62 ATOM 1065CD LYS A 140 −19.696 −3.693 −25.060 1.00 28.24 ATOM 1066 CE LYS A 140−18.589 −3.635 −24.056 1.00 28.19 ATOM 1067 NZ LYS A 140 −18.940 −2.725−22.954 1.00 26.78 ATOM 1068 C LYS A 140 −21.126 −5.001 −29.584 1.0024.17 ATOM 1069 O LYS A 140 −22.053 −5.823 −29.670 1.00 24.94 ATOM 1070N TRP A 141 −21.062 −3.898 −30.321 1.00 23.60 ATOM 1071 CA TRP A 141−22.054 −3.613 −31.338 1.00 24.29 ATOM 1072 CB TRP A 141 −21.847 −2.226−31.953 1.00 24.36 ATOM 1073 CG TRP A 141 −22.973 −1.833 −32.874 1.0024.25 ATOM 1074 CD1 TRP A 141 −24.113 −1.170 −32.531 1.00 25.06 ATOM1075 NE1 TRP A 141 −24.921 −1.016 −33.638 1.00 25.22 ATOM 1076 CE2 TRP A141 −24.302 −1.575 −34.722 1.00 24.07 ATOM 1077 CD2 TRP A 141 −23.078−2.115 −34.276 1.00 24.80 ATOM 1078 CE3 TRP A 141 −22.248 −2.766 −35.2031.00 25.40 ATOM 1079 CZ3 TRP A 141 −22.669 −2.858 −36.532 1.00 25.72ATOM 1080 CH2 TRP A 141 −23.891 −2.304 −36.940 1.00 24.95 ATOM 1081 CZ2TRP A 141 −24.721 −1.666 −36.051 1.00 25.14 ATOM 1082 C TRP A 141−22.078 −4.666 −32.448 1.00 24.47 ATOM 1083 O TRP A 141 −23.155 −5.152−32.831 1.00 24.52 ATOM 1084 N LEU A 142 −20.904 −4.991 −32.985 1.0024.39 ATOM 1085 CA LEU A 142 −20.806 −6.024 −34.010 1.00 25.05 ATOM 1086CB LEU A 142 −19.361 −6.199 −34.473 1.00 24.56 ATOM 1087 CG LEU A 142−18.754 −5.023 −35.252 1.00 24.44 ATOM 1088 CD1 LEU A 142 −17.274 −5.304−35.441 1.00 23.72 ATOM 1089 CD2 LEU A 142 −19.424 −4.793 −36.624 1.0025.76 ATOM 1090 C LEU A 142 −21.406 −7.364 −33.556 1.00 25.97 ATOM 1091O LEU A 142 −22.195 −7.966 −34.283 1.00 26.49 ATOM 1092 N ILE A 143−21.045 −7.814 −32.359 1.00 27.04 ATOM 1093 CA ILE A 143 −21.596 −9.040−31.792 1.00 28.46 ATOM 1094 CB ILE A 143 −20.959 −9.362 −30.425 1.0028.30 ATOM 1095 CG1 ILE A 143 −19.474 −9.722 −30.609 1.00 27.97 ATOM1096 CD1 ILE A 143 −18.707 −9.814 −29.301 1.00 29.85 ATOM 1097 CG2 ILE A143 −21.720 −10.494 −29.717 1.00 29.57 ATOM 1098 C ILE A 143 −23.124−8.992 −31.682 1.00 29.52 ATOM 1099 O ILE A 143 −23.813 −9.928 −32.1181.00 30.10 ATOM 1100 N ASN A 144 −23.655 −7.916 −31.111 1.00 30.37 ATOM1101 CA ASN A 144 −25.109 −7.768 −30.988 1.00 32.18 ATOM 1102 CB ASN A144 −25.479 −6.522 −30.186 1.00 32.73 ATOM 1103 CG ASN A 144 −26.960−6.489 −29.792 1.00 36.88 ATOM 1104 OD1 ASN A 144 −27.444 −7.350 −29.0411.00 42.25 ATOM 1105 ND2 ASN A 144 −27.685 −5.488 −30.291 1.00 40.10ATOM 1106 C ASN A 144 −25.820 −7.760 −32.341 1.00 32.17 ATOM 1107 O ASNA 144 −27.012 −8.029 −32.411 1.00 32.73 ATOM 1108 N ASN A 145 −25.094−7.460 −33.411 1.00 32.19 ATOM 1109 CA ASN A 145 −25.705 −7.403 −34.7261.00 32.78 ATOM 1110 CB ASN A 145 −25.526 −6.014 −35.331 1.00 33.16 ATOM1111 CG ASN A 145 −26.397 −4.986 −34.639 1.00 34.32 ATOM 1112 OD1 ASN A145 −27.576 −4.841 −34.969 1.00 37.42 ATOM 1113 ND2 ASN A 145 −25.834−4.289 −33.647 1.00 34.31 ATOM 1114 C ASN A 145 −25.285 −8.533 −35.6711.00 33.13 ATOM 1115 O ASN A 145 −25.412 −8.415 −36.902 1.00 33.03 ATOM1116 N ASN A 146 −24.789 −9.618 −35.065 1.00 33.43 ATOM 1117 CA ASN A146 −24.475 −10.885 −35.736 1.00 34.14 ATOM 1118 CB ASN A 146 −25.710−11.459 −36.461 1.00 34.85 ATOM 1119 CG ASN A 146 −26.994 −11.280−35.657 1.00 37.41 ATOM 1120 OD1 ASN A 146 −27.033 −11.543 −34.450 1.0041.43 ATOM 1121 ND2 ASN A 146 −28.047 −10.814 −36.321 1.00 41.54 ATOM1122 C ASN A 146 −23.266 −10.795 −36.652 1.00 33.92 ATOM 1123 O ASN A146 −23.216 −11.419 −37.724 1.00 33.76 ATOM 1124 N TYR A 147 −22.280−10.013 −36.221 1.00 32.92 ATOM 1125 CA TYR A 147 −21.049 −9.870 −36.9741.00 32.90 ATOM 1126 CB TYR A 147 −20.859 −8.423 −37.451 1.00 33.31 ATOM1127 CG TYR A 147 −21.966 −7.893 −38.339 1.00 33.29 ATOM 1128 CD1 TYR A147 −22.168 −8.410 −39.621 1.00 34.11 ATOM 1129 CE1 TYR A 147 −23.177−7.924 −40.438 1.00 34.19 ATOM 1130 CZ TYR A 147 −23.986 −6.888 −39.9831.00 34.10 ATOM 1131 OH TYR A 147 −24.987 −6.399 −40.794 1.00 35.08 ATOM1132 CE2 TYR A 147 −23.798 −6.345 −38.722 1.00 32.48 ATOM 1133 CD2 TYR A147 −22.792 −6.852 −37.906 1.00 32.03 ATOM 1134 C TYR A 147 −19.857−10.297 −36.138 1.00 32.74 ATOM 1135 O TYR A 147 −18.795 −9.710 −36.2421.00 32.03 ATOM 1136 N GLN A 148 −20.037 −11.325 −35.312 1.00 33.44 ATOM1137 CA GLN A 148 −18.977 −11.807 −34.427 1.00 34.39 ATOM 1138 CB GLN A148 −19.483 −12.971 −33.573 1.00 34.76 ATOM 1139 CG GLN A 148 −18.523−13.445 −32.481 1.00 35.56 ATOM 1140 CD GLN A 148 −19.216 −14.273−31.401 1.00 36.59 ATOM 1141 OE1 GLN A 148 −20.296 −13.913 −30.916 1.0041.20 ATOM 1142 NE2 GLN A 148 −18.589 −15.380 −31.008 1.00 38.65 ATOM1143 C GLN A 148 −17.690 −12.196 −35.176 1.00 34.46 ATOM 1144 O GLN A148 −16.582 −12.002 −34.654 1.00 34.20 ATOM 1145 N PHE A 149 −17.841−12.735 −36.391 1.00 34.19 ATOM 1146 CA PHE A 149 −16.696 −13.131−37.217 1.00 34.10 ATOM 1147 CB PHE A 149 −17.140 −13.804 −38.534 1.0035.60 ATOM 1148 CG PHE A 149 −18.346 −13.168 −39.193 1.00 38.70 ATOM1149 CD1 PHE A 149 −19.388 −13.976 −39.676 1.00 42.72 ATOM 1150 CE1 PHEA 149 −20.518 −13.417 −40.295 1.00 43.69 ATOM 1151 CZ PHE A 149 −20.615−12.019 −40.437 1.00 43.12 ATOM 1152 CE2 PHE A 149 −19.567 −11.188−39.953 1.00 43.20 ATOM 1153 CD2 PHE A 149 −18.451 −11.772 −39.341 1.0042.33 ATOM 1154 C PHE A 149 −15.746 −11.960 −37.517 1.00 32.49 ATOM 1155O PHE A 149 −14.528 −12.132 −37.548 1.00 32.23 ATOM 1156 N THR A 150−16.327 −10.789 −37.751 1.00 30.95 ATOM 1157 CA THR A 150 −15.570 −9.568−38.040 1.00 29.68 ATOM 1158 CB THR A 150 −16.512 −8.424 −38.445 1.0029.97 ATOM 1159 OG1 THR A 150 −17.162 −8.768 −39.673 1.00 30.58 ATOM1160 CG2 THR A 150 −15.758 −7.096 −38.637 1.00 29.18 ATOM 1161 C THR A150 −14.727 −9.203 −36.822 1.00 28.54 ATOM 1162 O THR A 150 −13.566−8.827 −36.965 1.00 28.38 ATOM 1163 N VAL A 151 −15.310 −9.354 −35.6361.00 27.23 ATOM 1164 CA VAL A 151 −14.597 −9.146 −34.374 1.00 26.78 ATOM1165 CB VAL A 151 −15.529 −9.352 −33.148 1.00 26.25 ATOM 1166 CG1 VAL A151 −14.752 −9.213 −31.832 1.00 26.50 ATOM 1167 CG2 VAL A 151 −16.690−8.361 −33.178 1.00 24.41 ATOM 1168 C VAL A 151 −13.384 −10.080 −34.3051.00 27.61 ATOM 1169 O VAL A 151 −12.246 −9.638 −34.106 1.00 26.67 ATOM1170 N SER A 152 −13.625 −11.375 −34.505 1.00 28.53 ATOM 1171 CA SER A152 −12.551 −12.369 −34.470 1.00 30.01 ATOM 1172 CB SER A 152 −13.102−13.759 −34.773 1.00 30.18 ATOM 1173 OG SER A 152 −13.612 −14.300−33.586 1.00 32.28 ATOM 1174 C SER A 152 −11.419 −12.091 −35.430 1.0030.23 ATOM 1175 O SER A 152 −10.250 −12.250 −35.090 1.00 30.95 ATOM 1176N ASN A 153 −11.762 −11.705 −36.641 1.00 31.46 ATOM 1177 CA ASN A 153−10.753 −11.624 −37.674 1.00 32.41 ATOM 1178 CB ASN A 153 −11.333−12.118 −38.997 1.00 33.62 ATOM 1179 CG ASN A 153 −11.791 −13.584−38.902 1.00 36.13 ATOM 1180 OD1 ASN A 153 −12.931 −13.918 −39.231 1.0040.99 ATOM 1181 ND2 ASN A 153 −10.917 −14.444 −38.383 1.00 37.61 ATOM1182 C ASN A 153 −10.060 −10.272 −37.787 1.00 32.10 ATOM 1183 O ASN A153 −8.850 −10.213 −38.020 1.00 32.79 ATOM 1184 N VAL A 154 −10.810−9.193 −37.577 1.00 30.55 ATOM 1185 CA VAL A 154 −10.251 −7.854 −37.7501.00 28.93 ATOM 1186 CB VAL A 154 −11.217 −6.925 −38.537 1.00 29.03 ATOM1187 CG1 VAL A 154 −10.565 −5.577 −38.827 1.00 29.23 ATOM 1188 CG2 VAL A154 −11.654 −7.585 −39.860 1.00 29.87 ATOM 1189 C VAL A 154 −9.824−7.211 −36.414 1.00 27.28 ATOM 1190 O VAL A 154 −8.722 −6.678 −36.3061.00 26.96 ATOM 1191 N ILE A 155 −10.685 −7.288 −35.403 1.00 25.13 ATOM1192 CA ILE A 155 −10.525 −6.459 −34.197 1.00 23.05 ATOM 1193 CB ILE A155 −11.900 −5.972 −33.670 1.00 23.10 ATOM 1194 CG1 ILE A 155 −12.596−5.128 −34.741 1.00 22.49 ATOM 1195 CD1 ILE A 155 −14.006 −4.680 −34.3751.00 22.72 ATOM 1196 CG2 ILE A 155 −11.731 −5.144 −32.399 1.00 23.05ATOM 1197 C ILE A 155 −9.710 −7.136 −33.092 1.00 22.44 ATOM 1198 O ILE A155 −8.789 −6.537 −32.533 1.00 21.14 ATOM 1199 N TRP A 156 −10.006−8.409 −32.822 1.00 21.48 ATOM 1200 CA TRP A 156 −9.392 −9.099 −31.6961.00 21.75 ATOM 1201 CB TRP A 156 −9.958 −10.520 −31.511 1.00 22.50 ATOM1202 CG TRP A 156 −9.298 −11.245 −30.371 1.00 23.43 ATOM 1203 CD1 TRP A156 −8.420 −12.298 −30.461 1.00 24.92 ATOM 1204 NE1 TRP A 156 −8.011−12.680 −29.198 1.00 24.85 ATOM 1205 CE2 TRP A 156 −8.600 −11.863−28.269 1.00 26.38 ATOM 1206 CD2 TRP A 156 −9.416 −10.941 −28.970 1.0025.03 ATOM 1207 CE3 TRP A 156 −10.139 −9.983 −28.236 1.00 25.01 ATOM1208 CZ3 TRP A 156 −10.024 −9.982 −26.844 1.00 24.30 ATOM 1209 CH2 TRP A156 −9.206 −10.910 −26.185 1.00 23.97 ATOM 1210 CZ2 TRP A 156 −8.495−11.861 −26.875 1.00 24.60 ATOM 1211 C TRP A 156 −7.845 −9.109 −31.6991.00 21.52 ATOM 1212 O TRP A 156 −7.235 −8.945 −30.648 1.00 21.78 ATOM1213 N PRO A 157 −7.209 −9.303 −32.870 1.00 21.66 ATOM 1214 CA PRO A 157−5.726 −9.258 −32.878 1.00 21.40 ATOM 1215 CB PRO A 157 −5.378 −9.459−34.360 1.00 21.26 ATOM 1216 CG PRO A 157 −6.583 −10.172 −34.955 1.0022.82 ATOM 1217 CD PRO A 157 −7.762 −9.596 −34.207 1.00 21.45 ATOM 1218C PRO A 157 −5.162 −7.898 −32.410 1.00 21.30 ATOM 1219 O PRO A 157−4.092 −7.837 −31.795 1.00 21.11 ATOM 1220 N ILE A 158 −5.881 −6.821−32.724 1.00 20.52 ATOM 1221 CA ILE A 158 −5.457 −5.467 −32.318 1.0019.93 ATOM 1222 CB ILE A 158 −6.273 −4.348 −33.034 1.00 19.73 ATOM 1223CG1 ILE A 158 −6.261 −4.527 −34.559 1.00 21.25 ATOM 1224 CD1 ILE A 158−7.229 −3.640 −35.351 1.00 20.03 ATOM 1225 CG2 ILE A 158 −5.686 −2.971−32.670 1.00 20.16 ATOM 1226 C ILE A 158 −5.632 −5.366 −30.816 1.0019.58 ATOM 1227 O ILE A 158 −4.701 −5.023 −30.081 1.00 19.04 ATOM 1228 NVAL A 159 −6.840 −5.704 −30.359 1.00 19.39 ATOM 1229 CA VAL A 159 −7.201−5.624 −28.953 1.00 19.15 ATOM 1230 CB VAL A 159 −8.687 −6.026 −28.7441.00 19.06 ATOM 1231 CG1 VAL A 159 −9.046 −6.028 −27.253 1.00 20.39 ATOM1232 CG2 VAL A 159 −9.604 −5.090 −29.511 1.00 20.08 ATOM 1233 C VAL A159 −6.280 −6.501 −28.105 1.00 19.39 ATOM 1234 O VAL A 159 −5.794 −6.089−27.036 1.00 18.63 ATOM 1235 N ARG A 160 −6.022 −7.721 −28.585 1.0018.93 ATOM 1236 CA ARG A 160 −5.171 −8.633 −27.833 1.00 19.64 ATOM 1237CB ARG A 160 −5.078 −10.005 −28.513 1.00 19.17 ATOM 1238 CG ARG A 160−4.064 −10.942 −27.872 1.00 21.41 ATOM 1239 CD ARG A 160 −3.978 −12.278−28.637 1.00 23.47 ATOM 1240 NE ARG A 160 −3.542 −12.066 −30.021 1.0029.25 ATOM 1241 CZ ARG A 160 −3.963 −12.771 −31.074 1.00 33.46 ATOM 1242NH1 ARG A 160 −4.839 −13.764 −30.929 1.00 36.48 ATOM 1243 NH2 ARG A 160−3.501 −12.489 −32.289 1.00 34.33 ATOM 1244 C ARG A 160 −3.785 −8.058−27.580 1.00 18.24 ATOM 1245 O ARG A 160 −3.262 −8.233 −26.517 1.0018.13 ATOM 1246 N ASN A 161 −3.182 −7.371 −28.551 1.00 18.57 ATOM 1247CA ASN A 161 −1.875 −6.717 −28.289 1.00 18.40 ATOM 1248 CB ASN A 161−1.344 −6.052 −29.561 1.00 18.82 ATOM 1249 CG ASN A 161 −0.772 −7.055−30.549 1.00 20.68 ATOM 1250 OD1 ASN A 161 −0.240 −8.097 −30.149 1.0022.60 ATOM 1251 ND2 ASN A 161 −0.883 −6.751 −31.837 1.00 19.81 ATOM 1252C ASN A 161 −1.946 −5.656 −27.182 1.00 18.36 ATOM 1253 O ASN A 161−1.078 −5.581 −26.313 1.00 17.42 ATOM 1254 N ASP A 162 −2.982 −4.816−27.233 1.00 17.86 ATOM 1255 CA ASP A 162 −3.163 −3.782 −26.194 1.0016.85 ATOM 1256 CB ASP A 162 −4.293 −2.821 −26.586 1.00 16.71 ATOM 1257CG ASP A 162 −3.851 −1.791 −27.623 1.00 17.46 ATOM 1258 OD1 ASP A 162−2.648 −1.440 −27.681 1.00 16.98 ATOM 1259 OD2 ASP A 162 −4.719 −1.333−28.388 1.00 18.89 ATOM 1260 C ASP A 162 −3.421 −4.354 −24.799 1.0016.51 ATOM 1261 O ASP A 162 −2.846 −3.897 −23.822 1.00 15.71 ATOM 1262 NLEU A 163 −4.278 −5.371 −24.715 1.00 16.83 ATOM 1263 CA LEU A 163 −4.532−6.071 −23.459 1.00 16.55 ATOM 1264 CB LEU A 163 −5.661 −7.088 −23.6371.00 16.96 ATOM 1265 CG LEU A 163 −7.030 −6.506 −23.975 1.00 19.29 ATOM1266 CD1 LEU A 163 −8.007 −7.663 −24.227 1.00 19.71 ATOM 1267 CD2 LEU A163 −7.484 −5.631 −22.818 1.00 21.19 ATOM 1268 C LEU A 163 −3.279 −6.750−22.883 1.00 16.19 ATOM 1269 O LEU A 163 −3.035 −6.690 −21.688 1.0015.47 ATOM 1270 N ASN A 164 −2.495 −7.401 −23.748 1.00 16.85 ATOM 1271CA ASN A 164 −1.251 −8.040 −23.305 1.00 16.44 ATOM 1272 CB ASN A 164−0.602 −8.836 −24.450 1.00 17.06 ATOM 1273 CG ASN A 164 −1.333 −10.153−24.718 1.00 19.63 ATOM 1274 OD1 ASN A 164 −2.274 −10.513 −23.982 1.0020.97 ATOM 1275 ND2 ASN A 164 −0.903 −10.881 −25.756 1.00 19.79 ATOM1276 C ASN A 164 −0.301 −7.022 −22.761 1.00 16.80 ATOM 1277 O ASN A 1640.349 −7.261 −21.751 1.00 15.97 ATOM 1278 N TYR A 165 −0.250 −5.860−23.415 1.00 16.45 ATOM 1279 CA TYR A 165 0.573 −4.744 −22.930 1.0016.15 ATOM 1280 CB TYR A 165 0.420 −3.508 −23.844 1.00 16.63 ATOM 1281CG TYR A 165 1.286 −2.356 −23.391 1.00 16.41 ATOM 1282 CD1 TYR A 1650.838 −1.459 −22.404 1.00 17.94 ATOM 1283 CE1 TYR A 165 1.651 −0.402−21.958 1.00 17.84 ATOM 1284 CZ TYR A 165 2.916 −0.223 −22.517 1.0018.36 ATOM 1285 OH TYR A 165 3.699 0.841 −22.091 1.00 16.54 ATOM 1286CE2 TYR A 165 3.383 −1.105 −23.502 1.00 16.73 ATOM 1287 CD2 TYR A 1652.552 −2.157 −23.942 1.00 16.01 ATOM 1288 C TYR A 165 0.198 −4.366−21.503 1.00 16.26 ATOM 1289 O TYR A 165 1.073 −4.218 −20.650 1.00 15.43ATOM 1290 N VAL A 166 −1.104 −4.177 −21.258 1.00 16.75 ATOM 1291 CA VALA 166 −1.600 −3.786 −19.933 1.00 17.39 ATOM 1292 CB VAL A 166 −3.124−3.479 −19.986 1.00 17.57 ATOM 1293 CG1 VAL A 166 −3.712 −3.197 −18.5821.00 19.25 ATOM 1294 CG2 VAL A 166 −3.363 −2.272 −20.909 1.00 16.49 ATOM1295 C VAL A 166 −1.258 −4.829 −18.865 1.00 17.83 ATOM 1296 O VAL A 166−0.741 −4.483 −17.792 1.00 18.00 ATOM 1297 N ALA A 167 −1.520 −6.099−19.188 1.00 18.26 ATOM 1298 CA ALA A 167 −1.233 −7.218 −18.285 1.0018.92 ATOM 1299 CB ALA A 167 −1.716 −8.532 −18.899 1.00 18.25 ATOM 1300C ALA A 167 0.251 −7.325 −17.956 1.00 19.08 ATOM 1301 O ALA A 167 0.611−7.757 −16.854 1.00 20.02 ATOM 1302 N GLN A 168 1.097 −6.955 −18.9201.00 19.13 ATOM 1303 CA GLN A 168 2.558 −7.022 −18.749 1.00 19.21 ATOM1304 CB GLN A 168 3.218 −7.201 −20.115 1.00 19.08 ATOM 1305 CG GLN A 1684.739 −7.373 −20.053 1.00 20.55 ATOM 1306 CD GLN A 168 5.337 −7.891−21.355 1.00 20.26 ATOM 1307 OE1 GLN A 168 4.634 −8.378 −22.238 1.0022.69 ATOM 1308 NE2 GLN A 168 6.643 −7.772 −21.476 1.00 23.10 ATOM 1309C GLN A 168 3.182 −5.807 −18.048 1.00 19.60 ATOM 1310 O GLN A 168 4.104−5.942 −17.205 1.00 18.87 ATOM 1311 N TYR A 169 2.709 −4.609 −18.4041.00 19.23 ATOM 1312 CA TYR A 169 3.399 −3.377 −18.011 1.00 19.45 ATOM1313 CB TYR A 169 3.760 −2.560 −19.266 1.00 20.43 ATOM 1314 CG TYR A 1694.773 −3.203 −20.203 1.00 21.30 ATOM 1315 CD1 TYR A 169 6.125 −3.243−19.872 1.00 23.63 ATOM 1316 CE1 TYR A 169 7.065 −3.822 −20.723 1.0024.59 ATOM 1317 CZ TYR A 169 6.651 −4.359 −21.926 1.00 23.11 ATOM 1318OH TYR A 169 7.580 −4.924 −22.779 1.00 25.26 ATOM 1319 CE2 TYR A 1695.309 −4.330 −22.288 1.00 22.49 ATOM 1320 CD2 TYR A 169 4.375 −3.754−21.422 1.00 20.87 ATOM 1321 C TYR A 169 2.675 −2.449 −17.015 1.00 19.49ATOM 1322 O TYR A 169 3.205 −1.386 −16.691 1.00 19.69 ATOM 1323 N TRP A170 1.508 −2.850 −16.498 1.00 18.91 ATOM 1324 CA TRP A 170 0.735 −1.981−15.588 1.00 19.29 ATOM 1325 CB TRP A 170 −0.610 −2.626 −15.208 1.0018.85 ATOM 1326 CG TRP A 170 −0.489 −3.743 −14.215 1.00 21.04 ATOM 1327CD1 TRP A 170 −0.342 −5.083 −14.489 1.00 20.67 ATOM 1328 NE1 TRP A 170−0.259 −5.793 −13.317 1.00 22.09 ATOM 1329 CE2 TRP A 170 −0.336 −4.928−12.258 1.00 19.19 ATOM 1330 CD2 TRP A 170 −0.481 −3.621 −12.789 1.0020.35 ATOM 1331 CE3 TRP A 170 −0.582 −2.530 −11.905 1.00 19.61 ATOM 1332CZ3 TRP A 170 −0.546 −2.769 −10.542 1.00 22.33 ATOM 1333 CH2 TRP A 170−0.404 −4.090 −10.038 1.00 21.08 ATOM 1334 CZ2 TRP A 170 −0.297 −5.179−10.884 1.00 20.76 ATOM 1335 C TRP A 170 1.526 −1.592 −14.336 1.00 19.20ATOM 1336 O TRP A 170 1.395 −0.475 −13.808 1.00 19.24 ATOM 1337 N ASN A171 2.371 −2.504 −13.858 1.00 19.13 ATOM 1338 CA ASN A 171 3.054 −2.280−12.596 1.00 20.12 ATOM 1339 CB ASN A 171 3.178 −3.603 −11.820 1.0020.59 ATOM 1340 CG ASN A 171 3.646 −3.419 −10.392 1.00 22.31 ATOM 1341OD1 ASN A 171 4.531 −4.155 −9.938 1.00 23.68 ATOM 1342 ND2 ASN A 1713.081 −2.435 −9.684 1.00 18.77 ATOM 1343 C ASN A 171 4.392 −1.557−12.797 1.00 20.93 ATOM 1344 O ASN A 171 5.333 −1.724 −12.022 1.00 20.35ATOM 1345 N GLN A 172 4.449 −0.712 −13.826 1.00 20.64 ATOM 1346 CA GLN A172 5.644 0.061 −14.156 1.00 22.31 ATOM 1347 CB GLN A 172 6.262 −0.452−15.469 1.00 22.04 ATOM 1348 CG GLN A 172 6.784 −1.895 −15.312 1.0025.79 ATOM 1349 CD GLN A 172 7.536 −2.450 −16.515 1.00 27.61 ATOM 1350OE1 GLN A 172 8.276 −1.735 −17.214 1.00 35.65 ATOM 1351 NE2 GLN A 1727.367 −3.755 −16.752 1.00 33.80 ATOM 1352 C GLN A 172 5.287 1.539−14.268 1.00 21.36 ATOM 1353 O GLN A 172 4.175 1.867 −14.704 1.00 21.04ATOM 1354 N THR A 173 6.209 2.417 −13.871 1.00 19.73 ATOM 1355 CA THR A173 5.948 3.871 −13.928 1.00 20.07 ATOM 1356 CB THR A 173 7.001 4.703−13.168 1.00 19.48 ATOM 1357 OG1 THR A 173 8.300 4.427 −13.707 1.0021.56 ATOM 1358 CG2 THR A 173 6.988 4.375 −11.690 1.00 20.86 ATOM 1359 CTHR A 173 5.913 4.347 −15.375 1.00 18.53 ATOM 1360 O THR A 173 6.3953.665 −16.292 1.00 18.48 ATOM 1361 N GLY A 174 5.345 5.528 −15.582 1.0018.38 ATOM 1362 CA GLY A 174 5.363 6.149 −16.903 1.00 17.13 ATOM 1363 CGLY A 174 4.760 7.522 −16.736 1.00 16.77 ATOM 1364 O GLY A 174 4.4627.939 −15.605 1.00 16.87 ATOM 1365 N PHE A 175 4.571 8.223 −17.849 1.0014.68 ATOM 1366 CA PHE A 175 4.004 9.577 −17.776 1.00 14.68 ATOM 1367 CBPHE A 175 4.522 10.432 −18.948 1.00 15.16 ATOM 1368 CG PHE A 175 5.94310.847 −18.756 1.00 15.28 ATOM 1369 CD1 PHE A 175 6.981 10.000 −19.1441.00 18.04 ATOM 1370 CE1 PHE A 175 8.313 10.359 −18.915 1.00 19.53 ATOM1371 CZ PHE A 175 8.609 11.582 −18.278 1.00 19.12 ATOM 1372 CE2 PHE A175 7.571 12.429 −17.876 1.00 18.63 ATOM 1373 CD2 PHE A 175 6.247 12.054−18.113 1.00 17.67 ATOM 1374 C PHE A 175 2.483 9.584 −17.655 1.00 14.11ATOM 1375 O PHE A 175 1.799 8.683 −18.175 1.00 14.32 ATOM 1376 N ASP A176 1.972 10.591 −16.938 1.00 14.79 ATOM 1377 CA ASP A 176 0.541 10.764−16.713 1.00 14.45 ATOM 1378 CB ASP A 176 0.297 11.661 −15.506 1.0013.51 ATOM 1379 CG ASP A 176 0.685 13.126 −15.760 1.00 14.99 ATOM 1380OD1 ASP A 176 1.774 13.399 −16.329 1.00 14.32 ATOM 1381 OD2 ASP A 176−0.112 14.012 −15.376 1.00 15.08 ATOM 1382 C ASP A 176 −0.143 11.343−17.962 1.00 14.21 ATOM 1383 O ASP A 176 0.525 11.641 −18.963 1.00 14.31ATOM 1384 N LEU A 177 −1.467 11.511 −17.891 1.00 13.30 ATOM 1385 CA LEUA 177 −2.235 11.981 −19.048 1.00 13.44 ATOM 1386 CB LEU A 177 −3.75211.839 −18.832 1.00 13.71 ATOM 1387 CG LEU A 177 −4.483 12.896 −18.0121.00 14.11 ATOM 1388 CD1 LEU A 177 −5.996 12.647 −18.061 1.00 13.65 ATOM1389 CD2 LEU A 177 −4.007 12.922 −16.553 1.00 14.74 ATOM 1390 C LEU A177 −1.884 13.424 −19.452 1.00 13.51 ATOM 1391 O LEU A 177 −2.131 13.813−20.600 1.00 13.74 ATOM 1392 N TRP A 178 −1.319 14.206 −18.521 1.0012.53 ATOM 1393 CA TRP A 178 −0.804 15.553 −18.855 1.00 12.95 ATOM 1394CB TRP A 178 −0.890 16.507 −17.660 1.00 12.67 ATOM 1395 CG TRP A 178−2.247 16.549 −17.005 1.00 13.10 ATOM 1396 CD1 TRP A 178 −2.504 16.508−15.662 1.00 13.10 ATOM 1397 NE1 TRP A 178 −3.856 16.568 −15.440 1.0012.14 ATOM 1398 CE2 TRP A 178 −4.501 16.646 −16.646 1.00 13.00 ATOM 1399CD2 TRP A 178 −3.516 16.641 −17.657 1.00 12.53 ATOM 1400 CE3 TRP A 178−3.919 16.715 −19.002 1.00 12.38 ATOM 1401 CZ3 TRP A 178 −5.309 16.813−19.290 1.00 13.91 ATOM 1402 CH2 TRP A 178 −6.262 16.804 −18.257 1.0013.52 ATOM 1403 CZ2 TRP A 178 −5.883 16.718 −16.930 1.00 13.97 ATOM 1404C TRP A 178 0.632 15.565 −19.400 1.00 13.35 ATOM 1405 O TRP A 178 1.14716.641 −19.756 1.00 13.76 ATOM 1406 N GLU A 179 1.255 14.387 −19.4471.00 13.33 ATOM 1407 CA GLU A 179 2.532 14.151 −20.117 1.00 13.32 ATOM1408 CB GLU A 179 2.503 14.632 −21.582 1.00 12.64 ATOM 1409 CG GLU A 1791.165 14.344 −22.280 1.00 13.03 ATOM 1410 CD GLU A 179 1.274 14.434−23.785 1.00 14.68 ATOM 1411 OE1 GLU A 179 0.895 15.478 −24.340 1.0015.98 ATOM 1412 OE2 GLU A 179 1.730 13.457 −24.405 1.00 15.44 ATOM 1413C GLU A 179 3.667 14.853 −19.374 1.00 15.00 ATOM 1414 O GLU A 179 4.62615.292 −20.004 1.00 14.90 ATOM 1415 N GLU A 180 3.561 14.932 −18.0481.00 14.78 ATOM 1416 CA GLU A 180 4.476 15.745 −17.246 1.00 16.76 ATOM1417 CB GLU A 180 3.719 16.928 −16.630 1.00 16.95 ATOM 1418 CG GLU A 1803.282 17.972 −17.654 1.00 18.69 ATOM 1419 CD GLU A 180 2.240 18.969−17.122 1.00 19.72 ATOM 1420 OE1 GLU A 180 1.587 18.715 −16.077 1.0019.00 ATOM 1421 OE2 GLU A 180 2.076 20.020 −17.793 1.00 24.62 ATOM 1422C GLU A 180 5.124 14.954 −16.104 1.00 16.50 ATOM 1423 O GLU A 180 6.26515.202 −15.750 1.00 17.36 ATOM 1424 N VAL A 181 4.364 14.056 −15.4881.00 16.77 ATOM 1425 CA VAL A 181 4.775 13.426 −14.218 1.00 16.87 ATOM1426 CB VAL A 181 3.672 13.555 −13.130 1.00 16.78 ATOM 1427 CG1 VAL A181 4.030 12.732 −11.893 1.00 18.56 ATOM 1428 CG2 VAL A 181 3.490 15.008−12.726 1.00 17.21 ATOM 1429 C VAL A 181 5.057 11.953 −14.451 1.00 17.22ATOM 1430 O VAL A 181 4.177 11.205 −14.825 1.00 16.93 ATOM 1431 N ASN A182 6.290 11.532 −14.201 1.00 18.39 ATOM 1432 CA ASN A 182 6.674 10.123−14.394 1.00 18.57 ATOM 1433 CB ASN A 182 8.136 10.079 −14.845 1.0019.77 ATOM 1434 CG ASN A 182 8.665 8.669 −15.056 1.00 23.96 ATOM 1435OD1 ASN A 182 9.881 8.470 −15.058 1.00 33.20 ATOM 1436 ND2 ASN A 1827.794 7.706 −15.258 1.00 23.63 ATOM 1437 C ASN A 182 6.440 9.375 −13.0731.00 18.31 ATOM 1438 O ASN A 182 7.132 9.621 −12.087 1.00 18.80 ATOM1439 N GLY A 183 5.436 8.508 −13.034 1.00 16.83 ATOM 1440 CA GLY A 1835.091 7.828 −11.790 1.00 15.98 ATOM 1441 C GLY A 183 3.989 6.837 −12.0331.00 15.59 ATOM 1442 O GLY A 183 3.937 6.228 −13.117 1.00 15.30 ATOM1443 N SER A 184 3.119 6.670 −11.035 1.00 14.95 ATOM 1444 CA SER A 1841.927 5.823 −11.151 1.00 15.45 ATOM 1445 CB SER A 184 1.844 4.792−10.017 1.00 15.76 ATOM 1446 OG SER A 184 2.998 3.935 −10.027 1.00 17.33ATOM 1447 C SER A 184 0.731 6.758 −11.073 1.00 15.14 ATOM 1448 O SER A184 0.646 7.546 −10.148 1.00 15.83 ATOM 1449 N SER A 185 −0.151 6.706−12.066 1.00 14.73 ATOM 1450 CA SER A 185 −1.169 7.755 −12.190 1.0013.87 ATOM 1451 CB SER A 185 −0.991 8.535 −13.515 1.00 14.73 ATOM 1452OG SER A 185 −1.793 9.721 −13.544 1.00 14.93 ATOM 1453 C SER A 185−2.551 7.140 −12.127 1.00 13.49 ATOM 1454 O SER A 185 −2.834 6.134−12.792 1.00 13.35 ATOM 1455 N PHE A 186 −3.427 7.782 −11.354 1.00 13.72ATOM 1456 CA PHE A 186 −4.764 7.275 −11.092 1.00 13.43 ATOM 1457 CB PHEA 186 −5.511 8.319 −10.260 1.00 13.58 ATOM 1458 CG PHE A 186 −6.8077.839 −9.662 1.00 13.52 ATOM 1459 CD1 PHE A 186 −6.819 6.873 −8.655 1.0016.11 ATOM 1460 CE1 PHE A 186 −8.004 6.489 −8.036 1.00 17.80 ATOM 1461CZ PHE A 186 −9.214 7.062 −8.442 1.00 16.18 ATOM 1462 CE2 PHE A 186−9.211 8.051 −9.432 1.00 15.77 ATOM 1463 CD2 PHE A 186 −8.003 8.435−10.030 1.00 14.62 ATOM 1464 C PHE A 186 −5.552 6.946 −12.372 1.00 13.57ATOM 1465 O PHE A 186 −6.053 5.839 −12.524 1.00 13.36 ATOM 1466 N PHE A187 −5.693 7.927 −13.267 1.00 12.53 ATOM 1467 CA PHE A 187 −6.416 7.762−14.527 1.00 12.84 ATOM 1468 CB PHE A 187 −6.284 9.056 −15.356 1.0011.69 ATOM 1469 CG PHE A 187 −6.949 9.016 −16.711 1.00 13.25 ATOM 1470CD1 PHE A 187 −8.284 9.338 −16.855 1.00 12.86 ATOM 1471 CE1 PHE A 187−8.893 9.342 −18.102 1.00 14.12 ATOM 1472 CZ PHE A 187 −8.139 9.041−19.236 1.00 14.05 ATOM 1473 CE2 PHE A 187 −6.806 8.721 −19.111 1.0014.30 ATOM 1474 CD2 PHE A 187 −6.206 8.711 −17.857 1.00 15.10 ATOM 1475C PHE A 187 −5.887 6.563 −15.318 1.00 12.69 ATOM 1476 O PHE A 187 −6.6665.837 −15.932 1.00 14.00 ATOM 1477 N THR A 188 −4.571 6.357 −15.294 1.0012.97 ATOM 1478 CA THR A 188 −3.938 5.302 −16.084 1.00 13.65 ATOM 1479CB THR A 188 −2.411 5.541 −16.104 1.00 13.69 ATOM 1480 OG1 THR A 188−2.158 6.789 −16.753 1.00 15.37 ATOM 1481 CG2 THR A 188 −1.648 4.432−16.833 1.00 13.24 ATOM 1482 C THR A 188 −4.284 3.929 −15.478 1.00 14.12ATOM 1483 O THR A 188 −4.766 3.039 −16.173 1.00 14.40 ATOM 1484 N VAL A189 −4.066 3.798 −14.173 1.00 13.34 ATOM 1485 CA VAL A 189 −4.348 2.543−13.446 1.00 14.76 ATOM 1486 CB VAL A 189 −3.893 2.612 −11.958 1.0014.90 ATOM 1487 CG1 VAL A 189 −4.331 1.334 −11.186 1.00 16.95 ATOM 1488CG2 VAL A 189 −2.374 2.799 −11.865 1.00 15.31 ATOM 1489 C VAL A 189−5.836 2.167 −13.560 1.00 14.48 ATOM 1490 O VAL A 189 −6.159 1.024−13.853 1.00 14.65 ATOM 1491 N ALA A 190 −6.732 3.146 −13.372 1.00 13.77ATOM 1492 CA ALA A 190 −8.171 2.858 −13.351 1.00 13.46 ATOM 1493 CB ALAA 190 −8.996 4.128 −12.922 1.00 12.74 ATOM 1494 C ALA A 190 −8.614 2.388−14.706 1.00 13.27 ATOM 1495 O ALA A 190 −9.432 1.479 −14.815 1.00 13.24ATOM 1496 N ASN A 191 −8.093 3.017 −15.760 1.00 12.50 ATOM 1497 CA ASN A191 −8.438 2.598 −17.127 1.00 13.01 ATOM 1498 CB ASN A 191 −8.122 3.707−18.137 1.00 12.65 ATOM 1499 CG ASN A 191 −9.191 4.781 −18.118 1.0014.08 ATOM 1500 OD1 ASN A 191 −10.319 4.541 −18.554 1.00 16.39 ATOM 1501ND2 ASN A 191 −8.857 5.955 −17.583 1.00 17.21 ATOM 1502 C ASN A 191−7.815 1.259 −17.521 1.00 13.93 ATOM 1503 O ASN A 191 −8.412 0.490−18.270 1.00 13.87 ATOM 1504 N GLN A 192 −6.636 0.995 −16.980 1.00 14.06ATOM 1505 CA GLN A 192 −5.988 −0.311 −17.139 1.00 14.96 ATOM 1506 CB GLNA 192 −4.575 −0.274 −16.552 1.00 14.33 ATOM 1507 CG GLN A 192 −3.5550.435 −17.500 1.00 13.64 ATOM 1508 CD GLN A 192 −2.206 0.635 −16.8571.00 15.33 ATOM 1509 OE1 GLN A 192 −2.074 0.568 −15.646 1.00 15.48 ATOM1510 NE2 GLN A 192 −1.182 0.925 −17.682 1.00 16.10 ATOM 1511 C GLN A 192−6.855 −1.411 −16.519 1.00 15.11 ATOM 1512 O GLN A 192 −7.076 −2.457−17.141 1.00 16.04 ATOM 1513 N HIS A 193 −7.398 −1.140 −15.329 1.0015.81 ATOM 1514 CA HIS A 193 −8.314 −2.069 −14.668 1.00 16.01 ATOM 1515CB HIS A 193 −8.746 −1.586 −13.281 1.00 16.72 ATOM 1516 CG HIS A 193−9.806 −2.454 −12.669 1.00 17.39 ATOM 1517 ND1 HIS A 193 −11.113 −2.039−12.505 1.00 18.05 ATOM 1518 CE1 HIS A 193 −11.821 −3.028 −11.983 1.0018.70 ATOM 1519 NE2 HIS A 193 −11.023 −4.071 −11.814 1.00 17.20 ATOM1520 CD2 HIS A 193 −9.758 −3.739 −12.242 1.00 18.04 ATOM 1521 C HIS A193 −9.536 −2.343 −15.521 1.00 15.85 ATOM 1522 O HIS A 193 −9.898 −3.501−15.732 1.00 15.70 ATOM 1523 N ARG A 194 −10.185 −1.285 −15.995 1.0015.27 ATOM 1524 CA ARG A 194 −11.349 −1.437 −16.852 1.00 15.29 ATOM 1525CB ARG A 194 −11.922 −0.073 −17.234 1.00 14.30 ATOM 1526 CG ARG A 194−13.029 −0.212 −18.239 1.00 14.46 ATOM 1527 CD ARG A 194 −13.614 1.102−18.723 1.00 15.43 ATOM 1528 NE ARG A 194 −14.589 0.780 −19.767 1.0015.58 ATOM 1529 CZ ARG A 194 −15.624 1.539 −20.125 1.00 17.92 ATOM 1530NH1 ARG A 194 −15.815 2.744 −19.576 1.00 14.60 ATOM 1531 NH2 ARG A 194−16.451 1.095 −21.060 1.00 16.15 ATOM 1532 C ARG A 194 −11.047 −2.258−18.111 1.00 15.74 ATOM 1533 O ARG A 194 −11.842 −3.120 −18.504 1.0015.56 ATOM 1534 N ALA A 195 −9.918 −1.967 −18.758 1.00 15.60 ATOM 1535CA ALA A 195 −9.562 −2.638 −20.004 1.00 15.90 ATOM 1536 CB ALA A 195−8.254 −2.042 −20.591 1.00 15.40 ATOM 1537 C ALA A 195 −9.436 −4.150−19.798 1.00 15.65 ATOM 1538 O ALA A 195 −9.959 −4.929 −20.610 1.0016.79 ATOM 1539 N LEU A 196 −8.763 −4.550 −18.721 1.00 16.36 ATOM 1540CA LEU A 196 −8.552 −5.976 −18.423 1.00 17.02 ATOM 1541 CB LEU A 196−7.625 −6.126 −17.235 1.00 16.96 ATOM 1542 CG LEU A 196 −6.167 −5.744−17.532 1.00 16.96 ATOM 1543 CD1 LEU A 196 −5.375 −5.857 −16.252 1.0018.93 ATOM 1544 CD2 LEU A 196 −5.590 −6.636 −18.630 1.00 20.38 ATOM 1545C LEU A 196 −9.877 −6.685 −18.167 1.00 17.92 ATOM 1546 O LEU A 196−10.102 −7.795 −18.643 1.00 18.98 ATOM 1547 N VAL A 197 −10.779 −6.014−17.454 1.00 18.51 ATOM 1548 CA VAL A 197 −12.112 −6.560 −17.181 1.0018.81 ATOM 1549 CB VAL A 197 −12.875 −5.702 −16.130 1.00 18.26 ATOM 1550CG1 VAL A 197 −14.340 −6.173 −15.994 1.00 21.18 ATOM 1551 CG2 VAL A 197−12.149 −5.784 −14.778 1.00 19.79 ATOM 1552 C VAL A 197 −12.924 −6.779−18.462 1.00 19.05 ATOM 1553 O VAL A 197 −13.456 −7.884 −18.693 1.0018.62 ATOM 1554 N GLU A 198 −13.010 −5.752 −19.308 1.00 18.43 ATOM 1555CA GLU A 198 −13.747 −5.873 −20.556 1.00 19.38 ATOM 1556 CB GLU A 198−13.849 −4.517 −21.241 1.00 19.38 ATOM 1557 CG GLU A 198 −14.609 −3.530−20.417 1.00 20.22 ATOM 1558 CD GLU A 198 −15.334 −2.537 −21.298 1.0022.66 ATOM 1559 OE1 GLU A 198 −16.313 −2.940 −21.940 1.00 22.16 ATOM1560 OE2 GLU A 198 −14.924 −1.369 −21.342 1.00 22.92 ATOM 1561 C GLU A198 −13.094 −6.861 −21.509 1.00 19.78 ATOM 1562 O GLU A 198 −13.780−7.506 −22.303 1.00 20.29 ATOM 1563 N GLY A 199 −11.770 −6.944 −21.4351.00 19.78 ATOM 1564 CA GLY A 199 −10.998 −7.823 −22.314 1.00 20.88 ATOM1565 C GLY A 199 −11.288 −9.285 −21.986 1.00 21.53 ATOM 1566 O GLY A 199−11.546 −10.083 −22.879 1.00 22.36 ATOM 1567 N ALA A 200 −11.256 −9.615−20.702 1.00 21.79 ATOM 1568 CA ALA A 200 −11.605 −10.956 −20.234 1.0022.44 ATOM 1569 CB ALA A 200 −11.463 −11.038 −18.728 1.00 22.21 ATOM1570 C ALA A 200 −13.016 −11.329 −20.696 1.00 22.54 ATOM 1571 O ALA A200 −13.237 −12.419 −21.214 1.00 22.25 ATOM 1572 N THR A 201 −13.965−10.403 −20.573 1.00 22.56 ATOM 1573 CA THR A 201 −15.345 −10.671−20.989 1.00 22.77 ATOM 1574 CB THR A 201 −16.302 −9.527 −20.551 1.0022.83 ATOM 1575 OG1 THR A 201 −16.219 −9.387 −19.134 1.00 24.92 ATOM1576 CG2 THR A 201 −17.756 −9.819 −20.929 1.00 23.76 ATOM 1577 C THR A201 −15.435 −10.905 −22.485 1.00 22.78 ATOM 1578 O THR A 201 −16.099−11.851 −22.925 1.00 22.95 ATOM 1579 N LEU A 202 −14.760 −10.069 −23.2751.00 21.78 ATOM 1580 CA LEU A 202 −14.805 −10.236 −24.717 1.00 22.62ATOM 1581 CB LEU A 202 −14.149 −9.055 −25.434 1.00 22.14 ATOM 1582 CGLEU A 202 −14.142 −9.107 −26.964 1.00 23.10 ATOM 1583 CD1 LEU A 202−15.544 −9.198 −27.564 1.00 24.20 ATOM 1584 CD2 LEU A 202 −13.346 −7.938−27.570 1.00 22.53 ATOM 1585 C LEU A 202 −14.139 −11.552 −25.151 1.0023.15 ATOM 1586 O LEU A 202 −14.649 −12.245 −26.036 1.00 22.90 ATOM 1587N ALA A 203 −13.019 −11.883 −24.510 1.00 23.38 ATOM 1588 CA ALA A 203−12.300 −13.129 −24.787 1.00 24.07 ATOM 1589 CB ALA A 203 −11.076−13.229 −23.913 1.00 23.57 ATOM 1590 C ALA A 203 −13.211 −14.354 −24.5691.00 24.38 ATOM 1591 O ALA A 203 −13.264 −15.244 −25.411 1.00 25.21 ATOM1592 N ALA A 204 −13.920 −14.363 −23.447 1.00 25.20 ATOM 1593 CA ALA A204 −14.849 −15.442 −23.093 1.00 26.63 ATOM 1594 CB ALA A 204 −15.450−15.186 −21.727 1.00 26.12 ATOM 1595 C ALA A 204 −15.939 −15.583 −24.1501.00 27.48 ATOM 1596 O ALA A 204 −16.267 −16.687 −24.564 1.00 28.39 ATOM1597 N THR A 205 −16.494 −14.461 −24.593 1.00 27.71 ATOM 1598 CA THR A205 −17.497 −14.470 −25.652 1.00 28.39 ATOM 1599 CB THR A 205 −18.088−13.051 −25.855 1.00 28.42 ATOM 1600 OG1 THR A 205 −18.669 −12.631−24.622 1.00 29.32 ATOM 1601 CG2 THR A 205 −19.150 −13.051 −26.932 1.0027.32 ATOM 1602 C THR A 205 −16.968 −15.004 −26.981 1.00 28.72 ATOM 1603O THR A 205 −17.697 −15.690 −27.719 1.00 29.06 ATOM 1604 N LEU A 206−15.712 −14.698 −27.288 1.00 28.58 ATOM 1605 CA LEU A 206 −15.122−15.122 −28.539 1.00 29.40 ATOM 1606 CB LEU A 206 −14.034 −14.144−29.001 1.00 29.40 ATOM 1607 CG LEU A 206 −14.438 −12.694 −29.322 1.0029.97 ATOM 1608 CD1 LEU A 206 −13.212 −11.899 −29.755 1.00 30.30 ATOM1609 CD2 LEU A 206 −15.561 −12.629 −30.375 1.00 29.58 ATOM 1610 C LEU A206 −14.540 −16.538 −28.489 1.00 29.55 ATOM 1611 O LEU A 206 −14.118−17.054 −29.521 1.00 30.16 ATOM 1612 N GLY A 207 −14.500 −17.145 −27.3071.00 30.30 ATOM 1613 CA GLY A 207 −13.786 −18.419 −27.122 1.00 30.91ATOM 1614 C GLY A 207 −12.294 −18.274 −27.375 1.00 31.55 ATOM 1615 O GLYA 207 −11.654 −19.173 −27.935 1.00 31.31 ATOM 1616 N GLN A 208 −11.746−17.115 −26.989 1.00 31.08 ATOM 1617 CA GLN A 208 −10.311 −16.877−27.031 1.00 31.10 ATOM 1618 CB GLN A 208 −9.999 −15.540 −27.703 1.0031.08 ATOM 1619 CG GLN A 208 −10.451 −15.455 −29.142 1.00 33.86 ATOM1620 CD GLN A 208 −9.469 −16.059 −30.126 1.00 38.19 ATOM 1621 OE1 GLN A208 −9.686 −15.999 −31.335 1.00 41.96 ATOM 1622 NE2 GLN A 208 −8.386−16.633 −29.626 1.00 38.96 ATOM 1623 C GLN A 208 −9.765 −16.909 −25.6111.00 30.45 ATOM 1624 O GLN A 208 −10.516 −17.048 −24.658 1.00 30.63 ATOM1625 N SER A 209 −8.451 −16.816 −25.469 1.00 29.96 ATOM 1626 CA SER A209 −7.841 −16.898 −24.160 1.00 30.04 ATOM 1627 CB SER A 209 −6.382−17.343 −24.297 1.00 30.04 ATOM 1628 OG SER A 209 −5.763 −17.371 −23.0301.00 32.75 ATOM 1629 C SER A 209 −7.948 −15.564 −23.409 1.00 29.53 ATOM1630 O SER A 209 −7.493 −14.532 −23.908 1.00 29.85 ATOM 1631 N GLY A 210−8.545 −15.594 −22.216 1.00 28.41 ATOM 1632 CA GLY A 210 −8.745 −14.368−21.401 1.00 27.16 ATOM 1633 C GLY A 210 −8.344 −14.480 −19.938 1.0026.83 ATOM 1634 O GLY A 210 −8.425 −13.498 −19.203 1.00 26.61 ATOM 1635N SER A 211 −7.888 −15.648 −19.497 1.00 25.85 ATOM 1636 CA SER A 211−7.651 −15.867 −18.067 1.00 25.26 ATOM 1637 CB SER A 211 −7.401 −17.353−17.783 1.00 25.87 ATOM 1638 OG SER A 211 −6.315 −17.789 −18.573 1.0026.62 ATOM 1639 C SER A 211 −6.509 −15.026 −17.498 1.00 24.55 ATOM 1640O SER A 211 −6.542 −14.676 −16.311 1.00 24.46 ATOM 1641 N ALA A 212−5.505 −14.712 −18.323 1.00 23.56 ATOM 1642 CA ALA A 212 −4.423 −13.816−17.906 1.00 23.42 ATOM 1643 CB ALA A 212 −3.417 −13.622 −19.031 1.0023.66 ATOM 1644 C ALA A 212 −4.999 −12.450 −17.496 1.00 23.54 ATOM 1645O ALA A 212 −4.566 −11.848 −16.513 1.00 24.00 ATOM 1646 N TYR A 213−5.970 −11.979 −18.271 1.00 22.79 ATOM 1647 CA TYR A 213 −6.594 −10.676−18.017 1.00 22.18 ATOM 1648 CB TYR A 213 −7.453 −10.241 −19.193 1.0021.74 ATOM 1649 CG TYR A 213 −6.761 −10.345 −20.515 1.00 20.05 ATOM 1650CD1 TYR A 213 −7.461 −10.761 −21.637 1.00 20.58 ATOM 1651 CE1 TYR A 213−6.854 −10.854 −22.868 1.00 21.95 ATOM 1652 CZ TYR A 213 −5.503 −10.545−22.988 1.00 20.62 ATOM 1653 OH TYR A 213 −4.930 −10.668 −24.220 1.0021.72 ATOM 1654 CE2 TYR A 213 −4.758 −10.149 −21.888 1.00 19.76 ATOM1655 CD2 TYR A 213 −5.400 −10.038 −20.647 1.00 20.61 ATOM 1656 C TYR A213 −7.423 −10.710 −16.758 1.00 23.06 ATOM 1657 O TYR A 213 −7.320−9.804 −15.939 1.00 22.56 ATOM 1658 N SER A 214 −8.226 −11.767 −16.5781.00 23.15 ATOM 1659 CA SER A 214 −9.064 −11.832 −15.392 1.00 23.90 ATOM1660 CB SER A 214 −10.244 −12.798 −15.580 1.00 24.54 ATOM 1661 OG SER A214 −9.776 −14.085 −15.939 1.00 27.95 ATOM 1662 C SER A 214 −8.259−12.122 −14.122 1.00 23.64 ATOM 1663 O SER A 214 −8.676 −11.762 −13.0261.00 23.43 ATOM 1664 N SER A 215 −7.095 −12.743 −14.248 1.00 23.82 ATOM1665 CA SER A 215 −6.295 −12.970 −13.050 1.00 24.66 ATOM 1666 CB SER A215 −5.390 −14.205 −13.200 1.00 25.70 ATOM 1667 OG SER A 215 −4.267−13.914 −14.004 1.00 29.15 ATOM 1668 C SER A 215 −5.491 −11.739 −12.6101.00 23.98 ATOM 1669 O SER A 215 −5.217 −11.561 −11.421 1.00 24.09 ATOM1670 N VAL A 216 −5.115 −10.894 −13.566 1.00 22.89 ATOM 1671 CA VAL A216 −4.347 −9.679 −13.272 1.00 22.50 ATOM 1672 CB VAL A 216 −3.442−9.296 −14.493 1.00 22.52 ATOM 1673 CG1 VAL A 216 −2.855 −7.888 −14.3691.00 24.11 ATOM 1674 CG2 VAL A 216 −2.296 −10.317 −14.652 1.00 22.49ATOM 1675 C VAL A 216 −5.256 −8.520 −12.801 1.00 21.88 ATOM 1676 O VAL A216 −4.869 −7.745 −11.936 1.00 21.84 ATOM 1677 N ALA A 217 −6.475 −8.440−13.332 1.00 21.86 ATOM 1678 CA ALA A 217 −7.374 −7.303 −13.050 1.0021.59 ATOM 1679 CB ALA A 217 −8.721 −7.479 −13.760 1.00 21.26 ATOM 1680C ALA A 217 −7.571 −6.968 −11.558 1.00 21.55 ATOM 1681 O ALA A 217−7.447 −5.804 −11.165 1.00 21.20 ATOM 1682 N PRO A 218 −7.842 −7.988−10.701 1.00 21.95 ATOM 1683 CA PRO A 218 −8.030 −7.700 −9.282 1.0021.59 ATOM 1684 CB PRO A 218 −8.283 −9.104 −8.670 1.00 22.29 ATOM 1685CG PRO A 218 −8.789 −9.905 −9.789 1.00 22.61 ATOM 1686 CD PRO A 218−7.966 −9.435 −10.963 1.00 22.11 ATOM 1687 C PRO A 218 −6.798 −7.065−8.634 1.00 21.27 ATOM 1688 O PRO A 218 −6.928 −6.299 −7.680 1.00 20.92ATOM 1689 N GLN A 219 −5.608 −7.386 −9.141 1.00 21.17 ATOM 1690 CA GLN A219 −4.378 −6.786 −8.609 1.00 21.51 ATOM 1691 CB GLN A 219 −3.149 −7.569−9.084 1.00 22.72 ATOM 1692 CG GLN A 219 −3.113 −8.985 −8.516 1.00 24.90ATOM 1693 CD GLN A 219 −3.323 −8.982 −7.015 1.00 29.57 ATOM 1694 OE1 GLNA 219 −2.715 −8.188 −6.288 1.00 31.58 ATOM 1695 NE2 GLN A 219 −4.207−9.843 −6.545 1.00 33.22 ATOM 1696 C GLN A 219 −4.240 −5.301 −8.996 1.0021.04 ATOM 1697 O GLN A 219 −3.687 −4.490 −8.229 1.00 21.07 ATOM 1698 NVAL A 220 −4.728 −4.973 −10.187 1.00 20.00 ATOM 1699 CA VAL A 220 −4.746−3.577 −10.630 1.00 19.34 ATOM 1700 CB VAL A 220 −5.098 −3.456 −12.1281.00 19.63 ATOM 1701 CG1 VAL A 220 −4.991 −2.000 −12.581 1.00 19.15 ATOM1702 CG2 VAL A 220 −4.162 −4.342 −12.974 1.00 17.97 ATOM 1703 C VAL A220 −5.730 −2.809 −9.737 1.00 19.65 ATOM 1704 O VAL A 220 −5.419 −1.728−9.257 1.00 18.97 ATOM 1705 N LEU A 221 −6.903 −3.391 −9.490 1.00 20.12ATOM 1706 CA LEU A 221 −7.895 −2.776 −8.620 1.00 20.83 ATOM 1707 CB LEUA 221 −9.180 −3.602 −8.599 1.00 20.48 ATOM 1708 CG LEU A 221 −10.336−2.991 −7.790 1.00 22.48 ATOM 1709 CD1 LEU A 221 −10.857 −1.726 −8.4581.00 22.33 ATOM 1710 CD2 LEU A 221 −11.430 −4.011 −7.637 1.00 22.51 ATOM1711 C LEU A 221 −7.360 −2.591 −7.192 1.00 21.44 ATOM 1712 O LEU A 221−7.617 −1.578 −6.539 1.00 20.45 ATOM 1713 N CYS A 222 −6.600 −3.572−6.718 1.00 22.60 ATOM 1714 CA CYS A 222 −5.957 −3.477 −5.415 1.00 22.10ATOM 1715 CB CYS A 222 −5.159 −4.749 −5.125 1.00 23.41 ATOM 1716 SG CYSA 222 −4.975 −5.000 −3.356 1.00 28.49 ATOM 1717 C CYS A 222 −5.035−2.270 −5.317 1.00 21.22 ATOM 1718 O CYS A 222 −5.060 −1.531 −4.331 1.0021.24 ATOM 1719 N PHE A 223 −4.210 −2.070 −6.347 1.00 20.11 ATOM 1720 CAPHE A 223 −3.287 −0.955 −6.368 1.00 19.03 ATOM 1721 CB PHE A 223 −2.334−1.108 −7.558 1.00 19.15 ATOM 1722 CG PHE A 223 −1.297 −0.011 −7.6691.00 19.23 ATOM 1723 CD1 PHE A 223 −0.576 0.410 −6.558 1.00 19.90 ATOM1724 CE1 PHE A 223 0.380 1.417 −6.661 1.00 20.91 ATOM 1725 CZ PHE A 2230.645 2.017 −7.902 1.00 21.07 ATOM 1726 CE2 PHE A 223 −0.061 1.598−9.024 1.00 18.81 ATOM 1727 CD2 PHE A 223 −1.022 0.581 −8.909 1.00 18.23ATOM 1728 C PHE A 223 −4.032 0.397 −6.423 1.00 18.38 ATOM 1729 O PHE A223 −3.597 1.376 −5.818 1.00 18.27 ATOM 1730 N LEU A 224 −5.148 0.428−7.142 1.00 18.45 ATOM 1731 CA LEU A 224 −5.957 1.665 −7.277 1.00 18.42ATOM 1732 CB LEU A 224 −7.208 1.403 −8.127 1.00 17.70 ATOM 1733 CG LEU A224 −7.990 2.645 −8.610 1.00 19.73 ATOM 1734 CD1 LEU A 224 −7.133 3.427−9.584 1.00 20.37 ATOM 1735 CD2 LEU A 224 −9.302 2.228 −9.264 1.00 18.64ATOM 1736 C LEU A 224 −6.385 2.226 −5.917 1.00 18.87 ATOM 1737 O LEU A224 −6.553 3.438 −5.757 1.00 18.45 ATOM 1738 N GLN A 225 −6.578 1.336−4.944 1.00 19.17 ATOM 1739 CA GLN A 225 −6.984 1.743 −3.585 1.00 20.00ATOM 1740 CB GLN A 225 −7.340 0.511 −2.725 1.00 20.26 ATOM 1741 CG GLN A225 −8.295 −0.463 −3.409 1.00 21.22 ATOM 1742 CD GLN A 225 −9.519 0.225−3.993 1.00 22.53 ATOM 1743 OE1 GLN A 225 −10.280 0.870 −3.262 1.0023.09 ATOM 1744 NE2 GLN A 225 −9.718 0.092 −5.302 1.00 19.33 ATOM 1745 CGLN A 225 −5.944 2.599 −2.871 1.00 20.19 ATOM 1746 O GLN A 225 −6.2993.399 −2.009 1.00 20.64 ATOM 1747 N ARG A 226 −4.678 2.450 −3.253 1.0020.51 ATOM 1748 CA ARG A 226 −3.564 3.144 −2.608 1.00 21.40 ATOM 1749 CBARG A 226 −2.219 2.505 −2.990 1.00 22.72 ATOM 1750 CG ARG A 226 −2.0811.010 −2.683 1.00 26.14 ATOM 1751 CD ARG A 226 −1.806 0.741 −1.204 1.0032.16 ATOM 1752 NE ARG A 226 −3.035 0.843 −0.432 1.00 37.77 ATOM 1753 CZARG A 226 −3.997 −0.079 −0.413 1.00 41.09 ATOM 1754 NH1 ARG A 226 −5.0930.120 0.322 1.00 42.17 ATOM 1755 NH2 ARG A 226 −3.874 −1.196 −1.127 1.0042.78 ATOM 1756 C ARG A 226 −3.499 4.645 −2.915 1.00 21.23 ATOM 1757 OARG A 226 −2.723 5.358 −2.288 1.00 20.95 ATOM 1758 N PHE A 227 −4.2985.123 −3.869 1.00 20.28 ATOM 1759 CA PHE A 227 −4.280 6.545 −4.250 1.0019.67 ATOM 1760 CB PHE A 227 −4.777 6.704 −5.693 1.00 19.40 ATOM 1761 CGPHE A 227 −3.814 6.195 −6.744 1.00 18.28 ATOM 1762 CD1 PHE A 227 −3.7334.831 −7.040 1.00 18.14 ATOM 1763 CE1 PHE A 227 −2.855 4.355 −8.046 1.0018.24 ATOM 1764 CZ PHE A 227 −2.034 5.264 −8.748 1.00 16.75 ATOM 1765CE2 PHE A 227 −2.113 6.641 −8.456 1.00 18.79 ATOM 1766 CD2 PHE A 227−3.005 7.091 −7.452 1.00 17.51 ATOM 1767 C PHE A 227 −5.126 7.435 −3.3431.00 20.55 ATOM 1768 O PHE A 227 −4.967 8.659 −3.334 1.00 20.38 ATOM1769 N TRP A 228 −6.032 6.820 −2.583 1.00 20.72 ATOM 1770 CA TRP A 228−6.924 7.545 −1.671 1.00 20.71 ATOM 1771 CB TRP A 228 −8.036 6.596−1.211 1.00 20.41 ATOM 1772 CG TRP A 228 −9.030 7.228 −0.283 1.00 20.59ATOM 1773 CD1 TRP A 228 −9.243 6.915 1.040 1.00 21.81 ATOM 1774 NE1 TRPA 228 −10.255 7.722 1.557 1.00 22.69 ATOM 1775 CE2 TRP A 228 −10.7128.553 0.565 1.00 20.71 ATOM 1776 CD2 TRP A 228 −9.958 8.280 −0.607 1.0018.88 ATOM 1777 CE3 TRP A 22B −10.225 9.014 −1.772 1.00 18.79 ATOM 1778CZ3 TRP A 228 −11.209 9.986 −1.734 1.00 20.13 ATOM 1779 CH2 TRP A 228−11.937 10.242 −0.552 1.00 21.18 ATOM 1780 CZ2 TRP A 228 −11.710 9.5370.601 1.00 21.65 ATOM 1781 C TRP A 228 −6.193 8.120 −0.463 1.00 21.38ATOM 1782 O TRP A 228 −5.479 7.394 0.236 1.00 21.50 ATOM 1783 N VAL A229 −6.379 9.416 −0.209 1.00 21.95 ATOM 1784 CA VAL A 229 −5.844 10.0650.983 1.00 22.99 ATOM 1785 CB VAL A 229 −5.205 11.436 0.654 1.00 22.81ATOM 1786 CG1 VAL A 229 −4.490 12.026 1.871 1.00 23.48 ATOM 1787 CG2 VALA 229 −4.226 11.292 −0.493 1.00 23.28 ATOM 1788 C VAL A 229 −6.98410.206 2.000 1.00 24.08 ATOM 1789 O VAL A 229 −7.803 11.119 1.899 1.0023.70 ATOM 1790 N SER A 230 −7.044 9.298 2.974 1.00 25.37 ATOM 1791 CASER A 230 −8.193 9.290 3.905 1.00 27.59 ATOM 1792 CB SER A 230 −8.2548.000 4.728 1.00 27.67 ATOM 1793 OG SER A 230 −7.029 7.805 5.402 1.0031.30 ATOM 1794 C SER A 230 −8.241 10.513 4.820 1.00 27.93 ATOM 1795 OSER A 230 −9.321 10.983 5.174 1.00 28.91 ATOM 1796 N SER A 231 −7.08811.059 5.165 1.00 28.76 ATOM 1797 CA SER A 231 −7.059 12.237 6.030 1.0029.72 ATOM 1798 CB SER A 231 −5.671 12.461 6.639 1.00 30.39 ATOM 1799 OGSER A 231 −4.703 12.713 5.635 1.00 34.43 ATOM 1800 C SER A 231 −7.56613.491 5.323 1.00 29.39 ATOM 1801 O SER A 231 −8.154 14.364 5.966 1.0030.97 ATOM 1802 N GLY A 232 −7.373 13.579 4.005 1.00 27.59 ATOM 1803 CAGLY A 232 −7.867 14.728 3.247 1.00 25.22 ATOM 1804 C GLY A 232 −9.18114.518 2.493 1.00 23.25 ATOM 1805 O GLY A 232 −9.810 15.487 2.077 1.0023.19 ATOM 1806 N GLY A 233 −9.589 13.265 2.320 1.00 20.97 ATOM 1807 CAGLY A 233 −10.809 12.937 1.578 1.00 19.35 ATOM 1808 C GLY A 233 −10.67313.226 0.094 1.00 18.83 ATOM 1809 O GLY A 233 −11.636 13.655 −0.561 1.0019.20 ATOM 1810 N TYR A 234 −9.487 12.977 −0.463 1.00 17.56 ATOM 1811 CATYR A 234 −9.309 13.155 −1.915 1.00 17.17 ATOM 1812 CB TYR A 234 −8.85114.584 −2.232 1.00 18.33 ATOM 1813 CG TYR A 234 −7.441 14.876 −1.7581.00 20.39 ATOM 1814 CD1 TYR A 234 −7.203 15.340 −0.454 1.00 20.72 ATOM1815 CE1 TYR A 234 −5.905 15.594 −0.018 1.00 24.11 ATOM 1816 CZ TYR A234 −4.840 15.399 −0.897 1.00 23.78 ATOM 1817 OH TYR A 234 −3.556 15.663−0.483 1.00 26.50 ATOM 1818 CE2 TYR A 234 −5.055 14.956 −2.187 1.0024.07 ATOM 1819 CD2 TYR A 234 −6.353 14.699 −2.611 1.00 20.58 ATOM 1820C TYR A 234 −8.318 12.141 −2.482 1.00 16.60 ATOM 1821 O TYR A 234 −7.61511.465 −1.735 1.00 16.29 ATOM 1822 N VAL A 235 −8.260 12.059 −3.805 1.0015.36 ATOM 1823 CA VAL A 235 −7.325 11.164 −4.472 1.00 15.62 ATOM 1824CB VAL A 235 −7.948 10.638 −5.798 1.00 15.96 ATOM 1825 CG1 VAL A 235−6.889 9.893 −6.645 1.00 17.31 ATOM 1826 CG2 VAL A 235 −9.134 9.723−5.506 1.00 15.87 ATOM 1827 C VAL A 235 −6.011 11.904 −4.742 1.00 15.54ATOM 1828 O VAL A 235 −6.006 12.998 −5.320 1.00 15.39 ATOM 1829 N ASP A236 −4.886 11.316 −4.325 1.00 15.24 ATOM 1830 CA ASP A 236 −3.580 11.837−4.705 1.00 15.22 ATOM 1831 CB ASP A 236 −2.533 11.431 −3.652 1.00 16.45ATOM 1832 CG ASP A 236 −1.145 11.922 −3.970 1.00 18.62 ATOM 1833 OD1 ASPA 236 −0.937 12.617 −4.992 1.00 17.17 ATOM 1834 OD2 ASP A 236 −0.22311.568 −3.182 1.00 22.79 ATOM 1835 C ASP A 236 −3.303 11.256 −6.098 1.0015.06 ATOM 1836 O ASP A 236 −3.088 10.040 −6.261 1.00 15.39 ATOM 1837 NSER A 237 −3.384 12.104 −7.125 1.00 14.24 ATOM 1838 CA SER A 237 −3.51811.587 −8.503 1.00 14.09 ATOM 1839 CB SER A 237 −4.000 12.697 −9.4461.00 13.76 ATOM 1840 OG SER A 237 −5.312 13.094 −9.070 1.00 14.52 ATOM1841 C SER A 237 −2.277 10.883 −9.053 1.00 14.22 ATOM 1842 O SER A 237−2.376 10.067 −9.965 1.00 13.80 ATOM 1843 N ASN A 238 −1.099 11.219−8.521 1.00 14.70 ATOM 1844 CA ASN A 238 0.116 10.547 −8.952 1.00 15.28ATOM 1845 CB ASN A 238 0.968 11.439 −9.856 1.00 14.84 ATOM 1846 CG ASN A238 0.277 11.742 −11.176 1.00 17.08 ATOM 1847 OD1 ASN A 238 0.244 10.901−12.072 1.00 16.61 ATOM 1848 ND2 ASN A 238 −0.308 12.932 −11.278 1.0016.63 ATOM 1849 C ASN A 238 0.912 10.150 −7.736 1.00 16.07 ATOM 1850 OASN A 238 1.169 10.988 −6.890 1.00 15.88 ATOM 1851 N ILE A 239 1.2808.875 −7.659 1.00 16.09 ATOM 1852 CA ILE A 239 2.125 8.410 −6.567 1.0018.07 ATOM 1853 CB ILE A 239 1.340 7.452 −5.600 1.00 17.66 ATOM 1854 CG1ILE A 239 0.893 6.180 −6.336 1.00 18.85 ATOM 1855 CD1 ILE A 239 0.1845.109 −5.437 1.00 19.02 ATOM 1856 CG2 ILE A 239 0.116 8.194 −4.974 1.0016.96 ATOM 1857 C ILE A 239 3.381 7.760 −7.169 1.00 19.32 ATOM 1858 OILE A 239 3.571 7.797 −8.392 1.00 19.19 ATOM 1859 N ASN A 240 4.2427.170 −6.329 1.00 20.56 ATOM 1860 CA ASN A 240 5.517 6.617 −6.823 1.0022.24 ATOM 1861 CB ASN A 240 5.275 5.385 −7.717 1.00 21.93 ATOM 1862 CGASN A 240 4.874 4.153 −6.926 1.00 24.19 ATOM 1863 OD1 ASN A 240 5.2693.995 −5.772 1.00 25.98 ATOM 1864 ND2 ASN A 240 4.083 3.278 −7.538 1.0022.26 ATOM 1865 C ASN A 240 6.334 7.677 −7.571 1.00 23.27 ATOM 1866 OASN A 240 7.000 7.381 −8.562 1.00 23.15 ATOM 1867 N THR A 241 6.2618.919 −7.096 1.00 25.02 ATOM 1868 CA THR A 241 6.939 10.038 −7.729 1.0028.12 ATOM 1869 CB THR A 241 6.044 10.720 −8.817 1.00 28.09 ATOM 1870OG1 THR A 241 6.741 11.836 −9.369 1.00 28.75 ATOM 1871 CG2 THR A 2414.727 11.208 −8.231 1.00 28.30 ATOM 1872 C THR A 241 7.302 11.065 −6.6741.00 29.96 ATOM 1873 O THR A 241 6.749 11.037 −5.589 1.00 30.58 ATOM1874 N ASN A 242 8.209 11.984 −6.991 1.00 33.17 ATOM 1875 CA ASN A 2428.585 13.019 −6.024 1.00 36.07 ATOM 1876 CB ASN A 242 10.059 12.880−5.616 1.00 37.13 ATOM 1877 CG ASN A 242 10.324 11.631 −4.771 1.00 40.96ATOM 1878 OD1 ASN A 242 9.509 11.235 −3.921 1.00 45.33 ATOM 1879 ND2 ASNA 242 11.477 11.007 −4.998 1.00 44.43 ATOM 1880 C ASN A 242 8.321 14.427−6.528 1.00 37.00 ATOM 1881 O ASN A 242 9.091 15.346 −6.245 1.00 37.94ATOM 1882 N GLU A 243 7.210 14.602 −7.233 1.00 37.54 ATOM 1883 CA GLU A243 6.895 15.869 −7.907 1.00 38.05 ATOM 1884 CB GLU A 243 5.775 15.638−8.925 1.00 38.77 ATOM 1885 CG GLU A 243 5.650 16.732 −9.977 1.00 42.65ATOM 1886 CD GLU A 243 6.959 16.985 −10.709 1.00 47.49 ATOM 1887 OE1 GLUA 243 7.424 16.084 −11.453 1.00 49.14 ATOM 1888 OE2 GLU A 243 7.52018.090 −10.532 1.00 50.15 ATOM 1889 C GLU A 243 6.559 17.088 −7.015 1.0037.15 ATOM 1890 O GLU A 243 6.645 18.240 −7.469 1.00 38.39 ATOM 1891 NGLY A 244 6.174 16.873 −5.766 1.00 35.69 ATOM 1892 CA GLY A 244 5.85818.019 −4.911 1.00 33.51 ATOM 1893 C GLY A 244 4.609 18.775 −5.369 1.0031.80 ATOM 1894 O GLY A 244 4.634 19.999 −5.535 1.00 33.32 ATOM 1895 NARG A 245 3.529 18.036 −5.612 1.00 27.92 ATOM 1896 CA ARG A 245 2.20018.618 −5.781 1.00 24.21 ATOM 1897 CB ARG A 245 1.638 18.224 −7.130 1.0024.30 ATOM 1898 CG ARG A 245 2.410 18.842 −8.275 1.00 24.62 ATOM 1899 CDARG A 245 1.625 18.681 −9.532 1.00 22.11 ATOM 1900 NE ARG A 245 2.46218.829 −10.713 1.00 21.13 ATOM 1901 CZ ARG A 245 2.114 18.302 −11.8781.00 21.50 ATOM 1902 NH1 ARG A 245 0.982 17.621 −11.945 1.00 18.57 ATOM1903 NH2 ARG A 245 2.883 18.443 −12.951 1.00 20.83 ATOM 1904 C ARG A 2451.295 18.040 −4.718 1.00 21.84 ATOM 1905 O ARG A 245 1.624 17.021 −4.1281.00 20.65 ATOM 1906 N THR A 246 0.140 18.652 −4.483 1.00 19.15 ATOM1907 CA THR A 246 −0.824 18.058 −3.540 1.00 17.46 ATOM 1908 CB THR A 246−1.989 18.997 −3.238 1.00 17.87 ATOM 1909 OG1 THR A 246 −2.752 19.155−4.440 1.00 15.85 ATOM 1910 CG2 THR A 246 −1.495 20.370 −2.730 1.0017.50 ATOM 1911 C THR A 246 −1.426 16.769 −4.103 1.00 17.25 ATOM 1912 OTHR A 246 −1.884 15.914 −3.351 1.00 17.57 ATOM 1913 N GLY A 247 −1.48216.646 −5.430 1.00 15.60 ATOM 1914 CA GLY A 247 −2.148 15.492 −6.0541.00 15.02 ATOM 1915 C GLY A 247 −3.609 15.761 −6.396 1.00 14.69 ATOM1916 O GLY A 247 −4.260 14.939 −7.059 1.00 14.45 ATOM 1917 N LYS A 248−4.137 16.890 −5.928 1.00 13.43 ATOM 1918 CA LYS A 248 −5.508 17.286−6.259 1.00 13.00 ATOM 1919 CB LYS A 248 −5.969 18.453 −5.396 1.00 12.32ATOM 1920 CG LYS A 248 −5.965 18.179 −3.881 1.00 13.12 ATOM 1921 CD LYSA 248 −6.133 19.493 −3.102 1.00 14.08 ATOM 1922 CE LYS A 248 −5.98519.253 −1.584 1.00 17.84 ATOM 1923 NZ LYS A 248 −6.335 20.492 −0.8351.00 16.74 ATOM 1924 C LYS A 248 −5.490 17.713 −7.736 1.00 12.73 ATOM1925 O LYS A 248 −4.866 18.707 −8.104 1.00 12.75 ATOM 1926 N ASP A 249−6.185 16.964 −8.580 1.00 11.92 ATOM 1927 CA ASP A 249 −5.958 17.098−10.024 1.00 11.16 ATOM 1928 CB ASP A 249 −4.761 16.199 −10.385 1.0010.83 ATOM 1929 CG ASP A 249 −4.268 16.349 −11.831 1.00 12.54 ATOM 1930OD1 ASP A 249 −5.078 16.422 −12.785 1.00 11.42 ATOM 1931 OD2 ASP A 249−3.025 16.342 −12.001 1.00 13.30 ATOM 1932 C ASP A 249 −7.232 16.577−10.662 1.00 11.38 ATOM 1933 O ASP A 249 −7.774 15.542 −10.236 1.0010.86 ATOM 1934 N VAL A 250 −7.700 17.265 −11.703 1.00 11.28 ATOM 1935CA VAL A 250 −8.885 16.793 −12.438 1.00 11.59 ATOM 1936 CB VAL A 250−9.366 17.859 −13.493 1.00 12.49 ATOM 1937 CG1 VAL A 250 −8.480 17.815−14.728 1.00 13.03 ATOM 1938 CG2 VAL A 250 −10.859 17.654 −13.852 1.0013.75 ATOM 1939 C VAL A 250 −8.711 15.386 −13.064 1.00 11.77 ATOM 1940 OVAL A 250 −9.698 14.750 −13.467 1.00 11.71 ATOM 1941 N ASN A 251 −7.46114.925 −13.168 1.00 10.73 ATOM 1942 CA ASN A 251 −7.131 13.491 −13.3781.00 11.20 ATOM 1943 CB ASN A 251 −5.699 13.265 −12.813 1.00 10.94 ATOM1944 CG ASN A 251 −5.221 11.810 −12.892 1.00 11.58 ATOM 1945 OD1 ASN A251 −5.986 10.864 −12.672 1.00 12.47 ATOM 1946 ND2 ASN A 251 −3.89811.639 −13.164 1.00 14.40 ATOM 1947 C ASN A 251 −8.151 12.560 −12.7061.00 10.99 ATOM 1948 O ASN A 251 −8.755 11.706 −13.355 1.00 11.49 ATOM1949 N SER A 252 −8.407 12.774 −11.417 1.00 11.45 ATOM 1950 CA SER A 252−9.293 11.876 −10.634 1.00 11.79 ATOM 1951 CB SER A 252 −9.062 12.155−9.149 1.00 13.31 ATOM 1952 OG SER A 252 −9.338 13.524 −8.882 1.00 13.41ATOM 1953 C SER A 252 −10.784 12.002 −10.996 1.00 11.39 ATOM 1954 O SERA 252 −11.532 11.023 −10.964 1.00 12.69 ATOM 1955 N VAL A 253 −11.19913.203 −11.383 1.00 10.56 ATOM 1956 CA VAL A 253 −12.582 13.459 −11.8211.00 10.70 ATOM 1957 CB VAL A 253 −12.884 15.004 −11.856 1.00 11.02 ATOM1958 CG1 VAL A 253 −14.335 15.262 −12.345 1.00 11.24 ATOM 1959 CG2 VAL A253 −12.711 15.585 −10.449 1.00 10.91 ATOM 1960 C VAL A 253 −12.61012.827 −13.187 1.00 11.38 ATOM 1961 O VAL A 253 −13.824 12.143 −13.4071.00 11.69 ATOM 1962 N LEU A 254 −11.866 13.059 −14.108 1.00 11.32 ATOM1963 CA LEU A 254 −11.891 12.393 −15.417 1.00 12.12 ATOM 1964 CB LEU A254 −10.635 12.759 −16.238 1.00 11.95 ATOM 1965 CG LEU A 254 −10.63414.202 −16.763 1.00 12.23 ATOM 1966 CD1 LEU A 254 −9.266 14.564 −17.3301.00 12.77 ATOM 1967 CD2 LEU A 254 −11.714 14.371 −17.845 1.00 15.26ATOM 1968 C LEU A 254 −11.963 10.872 −15.271 1.00 12.22 ATOM 1969 O LEUA 254 −12.675 10.201 −16.024 1.00 12.01 ATOM 1970 N THR A 255 −11.20810.338 −14.315 1.00 11.58 ATOM 1971 CA THR A 255 −11.219 8.913 −14.0421.00 12.53 ATOM 1972 CB THR A 255 −10.267 8.552 −12.890 1.00 12.83 ATOM1973 OG1 THR A 255 −8.935 8.933 −13.240 1.00 13.00 ATOM 1974 CG2 THR A255 −10.300 7.035 −12.634 1.00 15.06 ATOM 1975 C THR A 255 −12.632 8.448−13.705 1.00 13.12 ATOM 1976 O THR A 255 −13.131 7.467 −14.285 1.0013.49 ATOM 1977 N SER A 256 −13.289 9.158 −12.790 1.00 13.46 ATOM 1978CA SER A 256 −14.641 8.781 −12.343 1.00 12.85 ATOM 1979 CB SER A 256−15.152 9.760 −11.282 1.00 13.40 ATOM 1980 OG SER A 256 −16.332 9.252−10.674 1.00 16.69 ATOM 1981 C SER A 256 −15.610 8.705 −13.518 1.0013.13 ATOM 1982 O SER A 256 −16.360 7.711 −13.654 1.00 13.10 ATOM 1983 NILE A 257 −15.594 9.728 −14.377 1.00 12.32 ATOM 1984 CA ILE A 257−16.523 9.784 −15.513 1.00 12.32 ATOM 1985 CB ILE A 257 −16.747 11.215−16.072 1.00 11.55 ATOM 1986 CG1 ILE A 257 −15.482 11.773 −16.764 1.0011.38 ATOM 1987 CD1 ILE A 257 −15.699 13.143 −17.441 1.00 13.23 ATOM1988 CG2 ILE A 257 −17.257 12.166 −14.942 1.00 13.70 ATOM 1989 C ILE A257 −16.220 8.795 −16.653 1.00 12.79 ATOM 1990 O ILE A 257 −17.150 8.319−17.338 1.00 13.25 ATOM 1991 N HIS A 258 −14.941 8.487 −16.855 1.0012.71 ATOM 1992 CA HIS A 258 −14.565 7.566 −17.931 1.00 13.41 ATOM 1993CB HIS A 258 −13.194 7.947 −18.498 1.00 12.06 ATOM 1994 CG HIS A 258−13.268 9.175 −19.341 1.00 13.92 ATOM 1995 ND1 HIS A 258 −13.942 9.196−20.547 1.00 16.01 ATOM 1996 CE1 HIS A 258 −13.891 10.421 −21.047 1.0018.57 ATOM 1997 NE2 HIS A 258 −13.256 11.199 −20.189 1.00 14.08 ATOM1998 CD2 HIS A 258 −12.861 10.449 −19.108 1.00 13.51 ATOM 1999 C HIS A258 −14.649 6.091 −17.565 1.00 14.12 ATOM 2000 O HIS A 258 −14.645 5.239−18.454 1.00 14.90 ATOM 2001 N THR A 259 −14.752 5.801 −16.274 1.0013.93 ATOM 2002 CA THR A 259 −15.034 4.420 −15.807 1.00 14.91 ATOM 2003CB THR A 259 −13.933 3.856 −14.899 1.00 14.46 ATOM 2004 OG1 THR A 259−13.788 4.647 −13.705 1.00 15.66 ATOM 2005 CG2 THR A 259 −12.589 3.802−15.677 1.00 15.81 ATOM 2006 C THR A 259 −16.433 4.248 −15.173 1.0014.21 ATOM 2007 O THR A 259 −16.709 3.235 −14.546 1.00 14.95 ATOM 2008 NPHE A 260 −17.290 5.238 −15.367 1.00 14.76 ATOM 2009 CA PHE A 260−18.691 5.194 −14.926 1.00 15.13 ATOM 2010 CB PHE A 260 −19.377 6.492−15.379 1.00 15.81 ATOM 2011 CG PHE A 260 −20.886 6.508 −15.228 1.0015.47 ATOM 2012 CD1 PHE A 260 −21.505 6.188 −14.015 1.00 17.59 ATOM 2013CE1 PHE A 260 −22.903 6.259 −13.898 1.00 19.11 ATOM 2014 CZ PHE A 260−23.682 6.653 −14.991 1.00 17.18 ATOM 2015 CE2 PHE A 260 −23.082 6.994−16.178 1.00 18.04 ATOM 2016 CD2 PHE A 260 −21.679 6.917 −16.296 1.0017.22 ATOM 2017 C PHE A 260 −19.436 3.977 −15.475 1.00 15.55 ATOM 2018 OPHE A 260 −19.426 3.725 −16.684 1.00 15.81 ATOM 2019 N ASP A 261 −20.0933.235 −14.586 1.00 15.51 ATOM 2020 CA ASP A 261 −21.008 2.176 −15.0061.00 16.05 ATOM 2021 CB ASP A 261 −20.303 0.813 −15.015 1.00 16.46 ATOM2022 CG ASP A 261 −21.205 −0.321 −15.490 1.00 17.60 ATOM 2023 OD1 ASP A261 −22.440 −0.122 −15.579 1.00 18.97 ATOM 2024 OD2 ASP A 261 −20.656−1.404 −15.810 1.00 18.29 ATOM 2025 C ASP A 261 −22.117 2.185 −13.9721.00 16.30 ATOM 2026 O ASP A 261 −21.882 1.809 −12.840 1.00 15.53 ATOM2027 N PRO A 262 −23.320 2.610 −14.374 1.00 18.21 ATOM 2028 CA PRO A 262−24.438 2.716 −13.412 1.00 20.39 ATOM 2029 CB PRO A 262 −25.589 3.308−14.247 1.00 20.43 ATOM 2030 CG PRO A 262 −25.235 3.044 −15.669 1.0020.06 ATOM 2031 CD PRO A 262 −23.709 2.994 −15.734 1.00 17.40 ATOM 2032C PRO A 262 −24.815 1.382 −12.753 1.00 22.31 ATOM 2033 O PRO A 262−25.356 1.374 −11.622 1.00 22.24 ATOM 2034 N ASN A 263 −24.508 0.267−13.421 1.00 22.99 ATOM 2035 CA ASN A 263 −24.750 −1.048 −12.838 1.0025.42 ATOM 2036 CB ASN A 263 −24.574 −2.149 −13.890 1.00 26.62 ATOM 2037CG ASN A 263 −25.680 −2.128 −14.948 1.00 30.74 ATOM 2038 OD1 ASN A 263−26.688 −1.419 −14.814 1.00 35.92 ATOM 2039 ND2 ASN A 263 −25.490 −2.906−16.007 1.00 35.87 ATOM 2040 C ASN A 263 −23.894 −1.316 −11.598 1.0025.45 ATOM 2041 O ASN A 263 −24.210 −2.190 −10.795 1.00 26.56 ATOM 2042N LEU A 264 −22.835 −0.529 −11.413 1.00 24.54 ATOM 2043 CA LEU A 264−22.022 −0.616 −10.213 1.00 24.27 ATOM 2044 CB LEU A 264 −20.549 −0.287−10.520 1.00 24.43 ATOM 2045 CG LEU A 264 −19.752 −1.346 −11.288 1.0025.38 ATOM 2046 CD1 LEU A 264 −18.375 −0.809 −11.659 1.00 26.05 ATOM2047 CD2 LEU A 264 −19.619 −2.672 −10.523 1.00 26.24 ATOM 2048 C LEU A264 −22.542 0.273 −9.066 1.00 23.47 ATOM 2049 O LEU A 264 −21.956 0.292−7.988 1.00 23.97 ATOM 2050 N GLY A 265 −23.631 1.000 −9.292 1.00 23.32ATOM 2051 CA GLY A 265 −24.218 1.840 −8.237 1.00 22.74 ATOM 2052 C GLY A265 −23.204 2.843 −7.729 1.00 21.84 ATOM 2053 O GLY A 265 −22.416 3.373−8.510 1.00 22.83 ATOM 2054 N CYS A 266 −23.175 3.086 −6.424 1.00 21.37ATOM 2055 CA CYS A 266 −22.233 4.073 −5.883 1.00 21.00 ATOM 2056 CB CYSA 266 −22.947 5.049 −4.936 1.00 20.86 ATOM 2057 SG CYS A 266 −24.3475.912 −5.711 1.00 20.96 ATOM 2058 C CYS A 266 −20.992 3.427 −5.275 1.0020.98 ATOM 2059 O CYS A 266 −20.513 3.814 −4.203 1.00 21.01 ATOM 2060 NASP A 267 −20.462 2.443 −6.002 1.00 20.39 ATOM 2061 CA ASP A 267 −19.3031.686 −5.577 1.00 20.67 ATOM 2062 CB ASP A 267 −18.961 0.621 −6.618 1.0020.84 ATOM 2063 CG ASP A 267 −17.666 −0.101 −6.288 1.00 24.28 ATOM 2064OD1 ASP A 267 −16.852 −0.322 −7.200 1.00 25.84 ATOM 2065 OD2 ASP A 267−17.455 −0.407 −5.098 1.00 27.46 ATOM 2066 C ASP A 267 −18.072 2.567−5.391 1.00 19.78 ATOM 2067 O ASP A 267 −17.593 3.161 −6.353 1.00 18.61ATOM 2068 N ALA A 268 −17.544 2.621 −4.174 1.00 18.35 ATOM 2069 CA ALA A268 −16.315 3.395 −3.944 1.00 19.35 ATOM 2070 CB ALA A 268 −16.207 3.868−2.472 1.00 19.46 ATOM 2071 C ALA A 268 −15.017 2.701 −4.415 1.00 19.46ATOM 2072 O ALA A 268 −14.009 3.371 −4.665 1.00 19.42 ATOM 2073 N GLY A269 −15.029 1.370 −4.534 1.00 19.01 ATOM 2074 CA GLY A 269 −13.826 0.644−4.936 1.00 19.17 ATOM 2075 C GLY A 269 −13.370 1.032 −6.343 1.00 18.75ATOM 2076 O GLY A 269 −12.175 1.134 −6.624 1.00 19.54 ATOM 2077 N THR A270 −14.330 1.257 −7.230 1.00 17.92 ATOM 2078 CA THR A 270 −14.016 1.662−8.594 1.00 18.35 ATOM 2079 CB THR A 270 −14.852 0.882 −9.616 1.00 18.43ATOM 2080 OG1 THR A 270 −16.246 1.085 −9.350 1.00 18.51 ATOM 2081 CG2THR A 270 −14.529 −0.626 −9.555 1.00 19.75 ATOM 2082 C THR A 270 −14.2613.172 −8.771 1.00 18.25 ATOM 2083 O THR A 270 −14.326 3.674 −9.904 1.0017.88 ATOM 2084 N PHE A 271 −14.434 3.880 −7.650 1.00 17.17 ATOM 2085 CAPHE A 271 −14.531 5.359 −7.656 1.00 17.38 ATOM 2086 CB PHE A 271 −13.1835.965 −8.121 1.00 17.67 ATOM 2087 CG PHE A 271 −12.946 7.376 −7.673 1.0021.97 ATOM 2088 CD1 PHE A 271 −12.656 7.653 −6.337 1.00 24.90 ATOM 2089CE1 PHE A 271 −12.447 8.981 −5.923 1.00 24.46 ATOM 2090 CZ PHE A 271−12.474 10.043 −6.863 1.00 23.20 ATOM 2091 CE2 PHE A 271 −12.733 9.783−8.196 1.00 21.92 ATOM 2092 CD2 PHE A 271 −12.956 8.436 −8.599 1.0024.30 ATOM 2093 C PHE A 271 −15.677 5.856 −8.551 1.00 16.63 ATOM 2094 OPHE A 271 −15.479 6.764 −9.358 1.00 15.93 ATOM 2095 N GLN A 272 −16.8615.249 −8.439 1.00 15.21 ATOM 2096 CA GLN A 272 −18.011 5.673 −9.251 1.0014.97 ATOM 2097 CB GLN A 272 −19.227 4.755 −9.013 1.00 14.93 ATOM 2098CG GLN A 272 −19.021 3.355 −9.615 1.00 16.30 ATOM 2099 CD GLN A 272−18.755 3.413 −11.102 1.00 15.81 ATOM 2100 OE1 GLN A 272 −19.575 3.909−11.883 1.00 16.97 ATOM 2101 NE2 GLN A 272 −17.617 2.861 −11.512 1.0018.50 ATOM 2102 C GLN A 272 −18.402 7.118 −8.929 1.00 14.73 ATOM 2103 OGLN A 272 −18.194 7.555 −7.800 1.00 15.60 ATOM 2104 N PRO A 273 −18.9557.859 −9.914 1.00 14.45 ATOM 2105 CA PRO A 273 −19.342 9.255 −9.682 1.0014.57 ATOM 2106 CB PRO A 273 −20.157 9.597 −10.927 1.00 14.64 ATOM 2107CG PRO A 273 −19.443 8.767 −12.031 1.00 14.70 ATOM 2108 CD PRO A 273−19.156 7.458 −11.326 1.00 14.10 ATOM 2109 C PRO A 273 −20.162 9.542−8.407 1.00 15.22 ATOM 2110 O PRO A 273 −19.910 10.562 −7.752 1.00 15.03ATOM 2111 N CYS A 274 −21.130 8.682 −8.075 1.00 15.76 ATOM 2112 CA CYS A274 −21.926 8.913 −6.853 1.00 16.22 ATOM 2113 CB CYS A 274 −23.389 8.489−7.039 1.00 16.57 ATOM 2114 SG CYS A 274 −23.611 6.769 −7.423 1.00 17.39ATOM 2115 C CYS A 274 −21.331 8.281 −5.605 1.00 16.64 ATOM 2116 O CYS A274 −21.958 8.329 −4.529 1.00 16.55 ATOM 2117 N SER A 275 −20.137 7.681−5.715 1.00 15.61 ATOM 2118 CA SER A 275 −19.476 7.117 −4.528 1.00 15.81ATOM 2119 CB SER A 275 −18.244 6.253 −4.877 1.00 15.06 ATOM 2120 OG SERA 275 −17.144 7.041 −5.315 1.00 14.92 ATOM 2121 C SER A 275 −19.0978.232 −3.545 1.00 16.06 ATOM 2122 O SER A 275 −18.818 9.366 −3.949 1.0014.39 ATOM 2123 N ASP A 276 −19.103 7.919 −2.248 1.00 16.42 ATOM 2124 CAASP A 276 −18.731 8.935 −1.271 1.00 16.52 ATOM 2125 CB ASP A 276 −19.0208.511 0.189 1.00 16.27 ATOM 2126 CG ASP A 276 −18.244 7.281 0.656 1.0019.14 ATOM 2127 OD1 ASP A 276 −18.371 7.001 1.873 1.00 19.62 ATOM 2128OD2 ASP A 276 −17.544 6.593 −0.120 1.00 17.10 ATOM 2129 C ASP A 276−17.312 9.469 −1.492 1.00 16.17 ATOM 2130 O ASP A 276 −17.084 10.683−1.415 1.00 15.20 ATOM 2131 N LYS A 277 −16.381 8.577 −1.823 1.00 15.43ATOM 2132 CA LYS A 277 −14.994 8.982 −2.115 1.00 15.34 ATOM 2133 CB LYSA 277 −14.089 7.763 −2.326 1.00 15.23 ATOM 2134 CG LYS A 277 −13.9246.905 −1.059 1.00 17.01 ATOM 2135 CD LYS A 277 −12.752 5.929 −1.204 1.0021.20 ATOM 2136 CE LYS A 277 −12.662 5.017 0.015 1.00 22.94 ATOM 2137 NZLYS A 277 −11.533 4.067 −0.165 1.00 29.19 ATOM 2138 C LYS A 277 −14.9009.915 −3.324 1.00 14.30 ATOM 2139 O LYS A 277 −14.152 10.887 −3.288 1.0014.70 ATOM 2140 N ALA A 278 −15.644 9.620 −4.393 1.00 14.45 ATOM 2141 CAALA A 278 −15.588 10.464 −5.605 1.00 13.61 ATOM 2142 CB ALA A 278−16.250 9.775 −6.783 1.00 13.30 ATOM 2143 C ALA A 278 −16.210 11.827−5.357 1.00 13.50 ATOM 2144 O ALA A 278 −15.730 12.840 −5.864 1.00 13.02ATOM 2145 N LEU A 279 −17.283 11.855 −4.565 1.00 13.22 ATOM 2146 CA LEUA 279 −17.936 13.132 −4.239 1.00 12.92 ATOM 2147 CB LEU A 279 −19.32312.893 −3.625 1.00 13.21 ATOM 2148 CG LEU A 279 −20.384 12.358 −4.6011.00 13.94 ATOM 2149 CD1 LEU A 279 −21.707 11.969 −3.887 1.00 17.68 ATOM2150 CD2 LEU A 279 −20.653 13.319 −5.781 1.00 17.52 ATOM 2151 C LEU A279 −17.065 13.995 −3.348 1.00 12.84 ATOM 2152 O LEU A 279 −16.94115.203 −3.577 1.00 13.54 ATOM 2153 N SER A 280 −16.463 13.390 −2.3151.00 12.45 ATOM 2154 CA SER A 280 −15.502 14.106 −1.459 1.00 13.53 ATOM2155 CB SER A 280 −14.951 13.168 −0.364 1.00 13.65 ATOM 2156 OG SER A280 −14.008 13.863 0.468 1.00 15.07 ATOM 2157 C SER A 280 −14.332 14.672−2.285 1.00 14.09 ATOM 2158 O SER A 280 −13.925 15.856 −2.130 1.00 13.43ATOM 2159 N ASN A 281 −13.795 13.830 −3.166 1.00 13.27 ATOM 2160 CA ASNA 281 −12.690 14.257 −4.027 1.00 13.19 ATOM 2161 CB ASN A 281 −12.23913.078 −4.888 1.00 12.05 ATOM 2162 CG ASN A 281 −11.116 13.455 −5.8491.00 13.13 ATOM 2163 OD1 ASN A 281 −9.989 13.637 −5.446 1.00 13.26 ATOM2164 ND2 ASN A 281 −11.442 13.573 −7.124 1.00 11.63 ATOM 2165 C ASN A281 −13.096 15.432 −4.933 1.00 12.33 ATOM 2166 O ASN A 281 −12.33016.380 −5.109 1.00 13.49 ATOM 2167 N LEU A 282 −14.287 15.355 −5.5061.00 12.05 ATOM 2168 CA LEU A 282 −14.760 16.422 −6.376 1.00 13.21 ATOM2169 CB LEU A 282 −16.147 16.109 −6.949 1.00 12.17 ATOM 2170 CG LEU A282 −16.791 17.216 −7.820 1.00 14.57 ATOM 2171 CD1 LEU A 282 −16.01117.378 −9.126 1.00 16.58 ATOM 2172 CD2 LEU A 282 −18.241 16.863 −8.1701.00 15.68 ATOM 2173 C LEU A 282 −14.739 17.754 −5.638 1.00 12.69 ATOM2174 O LEU A 282 −14.201 18.735 −6.153 1.00 13.45 ATOM 2175 N LYS A 283−15.283 17.791 −4.415 1.00 12.75 ATOM 2176 CA LYS A 283 −15.306 19.026−3.656 1.00 12.89 ATOM 2177 CB LYS A 283 −16.079 18.860 −2.334 1.0012.90 ATOM 2178 CG LYS A 283 −15.912 20.089 −1.432 1.00 13.94 ATOM 2179CD LYS A 283 −16.909 20.076 −0.252 1.00 14.67 ATOM 2180 CE LYS A 283−16.530 21.136 0.797 1.00 13.67 ATOM 2181 NZ LYS A 283 −16.315 22.4890.212 1.00 19.03 ATOM 2182 C LYS A 283 −13.889 19.537 −3.385 1.00 12.43ATOM 2183 O LYS A 283 −13.612 20.710 −3.556 1.00 12.14 ATOM 2184 N VAL A284 −12.988 18.652 −2.966 1.00 12.02 ATOM 2185 CA VAL A 284 −11.62419.055 −2.633 1.00 12.77 ATOM 2186 CB VAL A 284 −10.845 17.875 −2.0141.00 13.17 ATOM 2187 CG1 VAL A 284 −9.320 18.169 −1.936 1.00 13.21 ATOM2188 CG2 VAL A 284 −11.391 17.557 −0.630 1.00 15.81 ATOM 2189 C VAL A284 −10.927 19.599 −3.881 1.00 12.74 ATOM 2190 O VAL A 284 −10.22820.636 −3.827 1.00 12.21 ATOM 2191 N VAL A 285 −11.153 18.927 −5.0121.00 11.54 ATOM 2192 CA VAL A 285 −10.560 19.389 −6.287 1.00 12.35 ATOM2193 CB VAL A 285 −10.694 18.330 −7.425 1.00 12.36 ATOM 2194 CG1 VAL A285 −10.316 18.944 −8.813 1.00 12.25 ATOM 2195 CG2 VAL A 285 −9.79517.104 −7.140 1.00 13.25 ATOM 2196 C VAL A 285 −11.130 20.770 −6.7121.00 12.08 ATOM 2197 O VAL A 285 −10.367 21.696 −6.989 1.00 12.60 ATOM2198 N VAL A 286 −12.452 20.913 −6.728 1.00 11.87 ATOM 2199 CA VAL A 286−13.089 22.196 −7.074 1.00 12.87 ATOM 2200 CB VAL A 286 −14.631 22.080−7.038 1.00 13.01 ATOM 2201 CG1 VAL A 286 −15.300 23.468 −7.140 1.0014.31 ATOM 2202 CG2 VAL A 286 −15.103 21.157 −8.200 1.00 14.42 ATOM 2203C VAL A 286 −12.586 23.324 −6.164 1.00 12.84 ATOM 2204 O VAL A 286−12.206 24.402 −6.635 1.00 13.75 ATOM 2205 N ASP A 287 −12.552 23.064−4.853 1.00 12.85 ATOM 2206 CA ASP A 287 −12.116 24.059 −3.870 1.0013.90 ATOM 2207 CB ASP A 287 −12.199 23.506 −2.440 1.00 13.12 ATOM 2208CG ASP A 287 −13.637 23.441 −1.924 1.00 16.00 ATOM 2209 OD1 ASP A 287−14.541 24.002 −2.583 1.00 16.20 ATOM 2210 OD2 ASP A 287 −13.857 22.835−0.858 1.00 16.76 ATOM 2211 C ASP A 287 −10.727 24.564 −4.136 1.00 14.28ATOM 2212 O ASP A 287 −10.425 25.722 −3.841 1.00 15.53 ATOM 2213 N SER A288 −9.862 23.709 −4.677 1.00 14.50 ATOM 2214 CA SER A 288 −8.478 24.093−4.949 1.00 −14.58 ATOM 2215 CB SER A 288 −7.625 22.843 −5.229 1.0014.15 ATOM 2216 OG SER A 288 −7.758 22.417 −6.565 1.00 13.73 ATOM 2217 CSER A 288 −8.326 25.186 −6.038 1.00 14.61 ATOM 2218 O SER A 288 −7.27425.847 −6.143 1.00 14.59 ATOM 2219 N PHE A 289 −9.392 25.416 −6.809 1.0013.99 ATOM 2220 CA PHE A 289 −9.419 26.447 −7.831 1.00 14.09 ATOM 2221CB PHE A 289 −9.994 25.882 −9.135 1.00 13.52 ATOM 2222 CG PHE A 289−9.169 24.807 −9.704 1.00 11.38 ATOM 2223 CD1 PHE A 289 −7.976 25.114−10.367 1.00 12.17 ATOM 2224 CE1 PHE A 289 −7.184 24.095 −10.905 1.0013.93 ATOM 2225 CZ PHE A 289 −7.572 22.783 −10.771 1.00 13.96 ATOM 2226CE2 PHE A 289 −8.756 22.452 −10.097 1.00 11.77 ATOM 2227 CD2 PHE A 289−9.555 23.472 −9.571 1.00 11.08 ATOM 2228 C PHE A 289 −10.219 27.698−7.491 1.00 14.73 ATOM 2229 O PHE A 289 −10.092 28.713 −8.189 1.00 14.71ATOM 2230 N ARG A 290 −11.054 27.621 −6.464 1.00 15.09 ATOM 2231 CA ARGA 290 −11.953 28.740 −6.140 1.00 16.64 ATOM 2232 CB ARG A 290 −12.84228.401 −4.936 1.00 15.99 ATOM 2233 CG ARG A 290 −13.913 27.375 −5.2301.00 15.65 ATOM 2234 CD ARG A 290 −14.821 27.163 −4.012 1.00 16.79 ATOM2235 NE ARG A 290 −15.843 26.172 −4.330 1.00 15.04 ATOM 2236 CZ ARG A290 −16.986 26.470 −4.933 1.00 17.22 ATOM 2237 NH1 ARG A 290 −17.24827.734 −5.243 1.00 15.41 ATOM 2238 NH2 ARG A 290 −17.855 25.511 −5.2391.00 15.94 ATOM 2239 C ARG A 290 −11.240 30.046 −5.864 1.00 18.04 ATOM2240 O ARG A 290 −11.690 31.125 −6.279 1.00 19.61 ATOM 2241 N SER A 291−10.150 29.984 −5.128 1.00 19.44 ATOM 2242 CA SER A 291 −9.571 31.246−4.667 1.00 21.57 ATOM 2243 CB SER A 291 −9.146 31.101 −3.212 1.00 22.18ATOM 2244 OG SER A 291 −7.998 30.284 −3.144 1.00 28.35 ATOM 2245 C SER A291 −8.423 31.762 −5.534 1.00 20.65 ATOM 2246 O SER A 291 −7.865 32.851−5.272 1.00 22.43 ATOM 2247 N ILE A 292 −8.066 31.019 −6.576 1.00 19.16ATOM 2248 CA ILE A 292 −6.855 31.367 −7.330 1.00 17.65 ATOM 2249 CB ILEA 292 −5.805 30.185 −7.408 1.00 18.07 ATOM 2250 CG1 ILE A 292 −6.37928.972 −8.194 1.00 17.67 ATOM 2251 CD1 ILE A 292 −5.315 27.924 −8.6491.00 17.27 ATOM 2252 CG2 ILE A 292 −5.341 29.795 −5.994 1.00 18.29 ATOM2253 C ILE A 292 −7.065 31.973 −8.708 1.00 17.20 ATOM 2254 O ILE A 292−6.136 32.563 −9.251 1.00 16.35 ATOM 2255 N TYR A 293 −8.252 31.797−9.290 1.00 15.85 ATOM 2256 CA TYR A 293 −8.509 32.304 −10.648 1.0015.83 ATOM 2257 CB TYR A 293 −9.301 31.270 −11.474 1.00 15.43 ATOM 2258CG TYR A 293 −8.571 30.014 −11.886 1.00 15.10 ATOM 2259 CD1 TYR A 293−7.183 29.960 −11.965 1.00 14.38 ATOM 2260 CE1 TYR A 293 −6.540 28.795−12.395 1.00 14.38 ATOM 2261 CZ TYR A 293 −7.306 27.685 −12.743 1.0014.90 ATOM 2262 OH TYR A 293 −6.700 26.522 −13.158 1.00 15.55 ATOM 2263CE2 TYR A 293 −8.670 27.722 −12.671 1.00 15.47 ATOM 2264 CD2 TYR A 293−9.298 28.875 −12.255 1.00 13.91 ATOM 2265 C TYR A 293 −9.351 33.581−10.591 1.00 15.69 ATOM 2266 O TYR A 293 −10.404 33.594 −9.942 1.0015.47 ATOM 2267 N GLY A 294 −8.892 34.629 −11.276 1.00 14.83 ATOM 2268CA GLY A 294 −9.641 35.899 −11.353 1.00 15.57 ATOM 2269 C GLY A 294−11.078 35.702 −11.858 1.00 15.93 ATOM 2270 O GLY A 294 −12.010 36.359−11.376 1.00 15.66 ATOM 2271 N VAL A 295 −11.288 34.773 −12.799 1.0015.60 ATOM 2272 CA VAL A 295 −12.651 34.520 −13.270 1.00 16.24 ATOM 2273CB VAL A 295 −12.753 33.561 −14.501 1.00 16.31 ATOM 2274 CG1 VAL A 295−12.170 34.195 −15.740 1.00 16.26 ATOM 2275 CG2 VAL A 295 −12.128 32.184−14.199 1.00 16.19 ATOM 2276 C VAL A 295 −13.596 34.013 −12.172 1.0016.97 ATOM 2277 O VAL A 295 −14.813 34.108 −12.320 1.00 18.03 ATOM 2278N ASN A 296 −13.047 33.463 −11.092 1.00 16.93 ATOM 2279 CA ASN A 296−13.876 32.920 −10.020 1.00 17.69 ATOM 2280 CB ASN A 296 −13.250 31.633−9.472 1.00 17.57 ATOM 2281 CG ASN A 296 −13.296 30.493 −10.482 1.0016.44 ATOM 2282 OD1 ASN A 296 −14.158 30.481 −11.356 1.00 17.29 ATOM2283 ND2 ASN A 296 −12.401 29.513 −10.336 1.00 15.99 ATOM 2284 C ASN A296 −14.187 33.915 −8.896 1.00 19.30 ATOM 2285 O ASN A 296 −14.94533.601 −7.979 1.00 19.07 ATOM 2286 N LYS A 297 −13.617 35.116 −9.0071.00 20.37 ATOM 2287 CA LYS A 297 −13.811 36.203 −8.038 1.00 22.43 ATOM2288 CB LYS A 297 −13.209 37.502 −8.584 1.00 22.90 ATOM 2289 CG LYS A297 −11.741 37.680 −8.316 1.00 30.03 ATOM 2290 CD LYS A 297 −11.40139.189 −8.309 1.00 35.34 ATOM 2291 CE LYS A 297 −12.247 39.913 −7.2551.00 39.86 ATOM 2292 NZ LYS A 297 −11.995 41.386 −7.178 1.00 42.72 ATOM2293 C LYS A 297 −15.275 36.453 −7.782 1.00 21.89 ATOM 2294 O LYS A 297−16.061 36.585 −8.712 1.00 21.96 ATOM 2295 N GLY A 298 −15.659 36.537−6.517 1.00 22.72 ATOM 2296 CA GLY A 298 −17.050 36.869 −6.219 1.0022.99 ATOM 2297 C GLY A 298 −18.043 35.720 −6.278 1.00 23.54 ATOM 2298 OGLY A 298 −19.180 35.885 −5.855 1.00 25.04 ATOM 2299 N ILE A 299 −17.64734.546 −6.784 1.00 22.16 ATOM 2300 CA ILE A 299 −18.574 33.393 −6.7631.00 21.47 ATOM 2301 CB ILE A 299 −18.251 32.350 −7.884 1.00 21.22 ATOM2302 CG1 ILE A 299 −18.356 32.985 −9.274 1.00 19.64 ATOM 2303 CD1 ILE A299 −17.740 32.095 −10.415 1.00 19.76 ATOM 2304 CG2 ILE A 299 −19.16331.091 −7.762 1.00 20.54 ATOM 2305 C ILE A 299 −18.562 32.740 −5.3751.00 22.34 ATOM 2306 O ILE A 299 −17.486 32.395 −4.861 1.00 22.29 ATOM2307 N PRO A 300 −19.743 32.580 −4.751 1.00 23.04 ATOM 2308 CA PRO A 300−19.791 32.018 −3.392 1.00 23.60 ATOM 2309 CB PRO A 300 −21.217 32.364−2.922 1.00 24.19 ATOM 2310 CG PRO A 300 −22.015 32.437 −4.178 1.0023.80 ATOM 2311 CD PRO A 300 −21.085 32.934 −5.253 1.00 23.06 ATOM 2312C PRO A 300 −19.584 30.500 −3.322 1.00 23.50 ATOM 2313 O PRO A 300−19.664 29.810 −4.347 1.00 22.46 ATOM 2314 N ALA A 301 −19.325 29.985−2.116 1.00 22.68 ATOM 2315 CA ALA A 301 −19.380 28.549 −1.905 1.0022.89 ATOM 2316 CB ALA A 301 −18.988 28.185 −0.465 1.00 23.54 ATOM 2317C ALA A 301 −20.788 28.074 −2.236 1.00 21.91 ATOM 2318 O ALA A 301−21.759 28.834 −2.108 1.00 23.09 ATOM 2319 N GLY A 302 −20.898 26.838−2.698 1.00 20.96 ATOM 2320 CA GLY A 302 −22.173 26.272 −3.115 1.0019.69 ATOM 2321 C GLY A 302 −22.565 26.637 −4.537 1.00 19.78 ATOM 2322 OGLY A 302 −23.661 26.283 −4.991 1.00 19.32 ATOM 2323 N ALA A 303 −21.68627.355 −5.235 1.00 17.97 ATOM 2324 CA ALA A 303 −21.948 27.708 −6.6351.00 17.13 ATOM 2325 CB ALA A 303 −22.168 29.212 −6.812 1.00 16.73 ATOM2326 C ALA A 303 −20.784 27.245 −7.481 1.00 16.19 ATOM 2327 O ALA A 303−19.647 27.171 −7.004 1.00 16.23 ATOM 2328 N ALA A 304 −21.067 26.956−8.746 1.00 15.66 ATOM 2329 CA ALA A 304 −20.069 26.378 −9.640 1.0015.10 ATOM 2330 CB ALA A 304 −20.750 25.795 −10.860 1.00 15.80 ATOM 2331C ALA A 304 −19.002 27.394 −10.044 1.00 14.74 ATOM 2332 O ALA A 304−19.270 28.587 −10.121 1.00 14.27 ATOM 2333 N VAL A 305 −17.783 26.914−10.300 1.00 14.18 ATOM 2334 CA VAL A 305 −16.680 27.783 −10.698 1.0013.54 ATOM 2335 CB VAL A 305 −15.656 27.971 −9.543 1.00 13.42 ATOM 2336CG1 VAL A 305 −16.224 28.881 −8.418 1.00 14.25 ATOM 2337 CG2 VAL A 305−15.218 26.597 −8.966 1.00 14.99 ATOM 2338 C VAL A 305 −15.952 27.141−11.873 1.00 13.34 ATOM 2339 O VAL A 305 −16.121 25.944 −12.126 1.0012.46 ATOM 2340 N ALA A 306 −15.130 27.921 −12.562 1.00 13.38 ATOM 2341CA ALA A 306 −14.233 27.376 −13.573 1.00 14.37 ATOM 2342 CB ALA A 306−13.709 28.504 −14.470 1.00 15.32 ATOM 2343 C ALA A 306 −13.082 26.626−12.938 1.00 14.68 ATOM 2344 O ALA A 306 −12.457 27.116 −11.974 1.0015.21 ATOM 2345 N ILE A 307 −12.781 25.452 −13.484 1.00 13.50 ATOM 2346CA ILE A 307 −11.667 24.668 −12.975 1.00 13.67 ATOM 2347 CB ILE A 307−12.134 23.438 −12.163 1.00 14.45 ATOM 2348 CG1 ILE A 307 −12.756 22.386−13.072 1.00 15.37 ATOM 2349 CD1 ILE A 307 −12.921 21.033 −12.368 1.0019.15 ATOM 2350 CG2 ILE A 307 −13.119 23.848 −11.005 1.00 15.52 ATOM2351 C ILE A 307 −10.646 24.290 −14.059 1.00 12.52 ATOM 2352 O ILE A 307−10.974 24.232 −15.264 1.00 12.22 ATOM 2353 N GLY A 308 −9.405 24.095−13.604 1.00 11.71 ATOM 2354 CA GLY A 308 −8.276 23.737 −14.452 1.0011.64 ATOM 2355 C GLY A 308 −7.853 22.306 −14.199 1.00 11.62 ATOM 2356 OGLY A 308 −8.667 21.444 −13.806 1.00 12.05 ATOM 2357 N ARG A 309 −6.58322.026 −14.454 1.00 11.39 ATOM 2358 CA ARG A 309 −6.091 20.661 −14.3371.00 11.23 ATOM 2359 CB ARG A 309 −4.896 20.467 −15.275 1.00 11.37 ATOM2360 CG ARG A 309 −5.220 20.697 −16.791 1.00 11.29 ATOM 2361 CD ARG A309 −4.066 20.130 −17.625 1.00 12.62 ATOM 2362 NE ARG A 309 −2.84520.919 −17.425 1.00 12.15 ATOM 2363 CZ ARG A 309 −1.701 20.665 −18.0471.00 15.00 ATOM 2364 NH1 ARG A 309 −1.630 19.633 −18.910 1.00 12.05 ATOM2365 NH2 ARG A 309 −0.624 21.395 −17.778 1.00 13.85 ATOM 2366 C ARG A309 −5.654 20.425 −12.888 1.00 11.83 ATOM 2367 O ARG A 309 −6.093 19.481−12.221 1.00 11.38 ATOM 2368 N TYR A 310 −4.806 21.322 −12.399 1.0011.88 ATOM 2369 CA TYR A 310 −4.293 21.215 −11.022 1.00 11.17 ATOM 2370CB TYR A 310 −3.225 20.082 −10.878 1.00 12.49 ATOM 2371 CG TYR A 310−2.065 20.201 −11.844 1.00 13.10 ATOM 2372 CD1 TYR A 310 −2.128 19.622−13.138 1.00 12.57 ATOM 2373 CE1 TYR A 310 −1.069 19.772 −14.039 1.0015.63 ATOM 2374 CZ TYR A 310 0.065 20.475 −13.649 1.00 14.31 ATOM 2375OH TYR A 310 1.119 20.611 −14.529 1.00 14.42 ATOM 2376 CE2 TYR A 3100.159 21.030 −12.379 1.00 12.68 ATOM 2377 CD2 TYR A 310 −0.909 20.906−11.485 1.00 14.04 ATOM 2378 C TYR A 310 −3.779 22.596 −10.644 1.0012.74 ATOM 2379 O TYR A 310 −3.333 23.356 −11.505 1.00 12.44 ATOM 2380 NALA A 311 −3.872 22.945 −9.362 1.00 11.99 ATOM 2381 CA ALA A 311 −3.61824.337 −8.975 1.00 13.33 ATOM 2382 CB ALA A 311 −4.084 24.589 −7.5081.00 12.813 ATOM 2383 C ALA A 311 −2.157 24.768 −9.197 1.00 13.50 ATOM2384 O ALA A 311 −1.906 25.951 −9.468 1.00 14.52 ATOM 2385 N GLU A 312−1.216 23.823 −9.140 1.00 13.52 ATOM 2386 CA GLU A 312 0.219 24.134−9.332 1.00 14.23 ATOM 2387 CB GLU A 312 1.111 23.020 −8.790 1.00 15.44ATOM 2388 CG GLU A 312 0.933 22.802 −7.303 1.00 16.54 ATOM 2389 CD GLU A312 −0.130 21.762 −6.950 1.00 18.91 ATOM 2390 OE1 GLU A 312 −0.94121.338 −7.808 1.00 16.89 ATOM 2391 OE2 GLU A 312 −0.150 21.345 −5.7781.00 18.72 ATOM 2392 C GLU A 312 0.591 24.380 −10.796 1.00 14.80 ATOM2393 O GLU A 312 1.741 24.736 −11.100 1.00 14.98 ATOM 2394 N ASP A 313−0.374 24.197 −11.697 1.00 13.37 ATOM 2395 CA ASP A 313 −0.112 24.258−13.155 1.00 13.71 ATOM 2396 CB ASP A 313 −1.457 24.079 −13.888 1.0012.88 ATOM 2397 CG ASP A 313 −1.320 23.671 −15.343 1.00 14.44 ATOM 2398OD1 ASP A 313 −0.197 23.597 −15.900 1.00 13.19 ATOM 2399 OD2 ASP A 313−2.400 23.406 −15.923 1.00 13.61 ATOM 2400 C ASP A 313 0.512 25.589−13.587 1.00 14.00 ATOM 2401 O ASP A 313 0.007 26.662 −13.219 1.00 14.35ATOM 2402 N VAL A 314 1.577 25.530 −14.399 1.00 13.84 ATOM 2403 CA VAL A314 2.145 26.747 −14.988 1.00 15.19 ATOM 2404 CB VAL A 314 3.602 27.016−14.520 1.00 16.70 ATOM 2405 CG1 VAL A 314 3.638 27.295 −13.009 1.0017.94 ATOM 2406 CG2 VAL A 314 4.551 25.857 −14.915 1.00 16.69 ATOM 2407C VAL A 314 2.123 26.729 −16.528 1.00 15.30 ATOM 2408 O VAL A 314 2.71227.598 −17.165 1.00 15.13 ATOM 2409 N TYR A 315 1.441 25.743 −17.1111.00 14.51 ATOM 2410 CA TYR A 315 1.351 25.634 −18.580 1.00 15.65 ATOM2411 CB TYR A 315 0.768 24.264 −18.957 1.00 15.82 ATOM 2412 CG TYR A 3150.694 23.988 −20.457 1.00 16.29 ATOM 2413 CD1 TYR A 315 1.824 24.124−21.265 1.00 17.01 ATOM 2414 CE1 TYR A 315 1.778 23.859 −22.634 1.0018.92 ATOM 2415 CZ TYR A 315 0.588 23.421 −23.208 1.00 16.14 ATOM 2416OH TYR A 315 0.557 23.164 −24.577 1.00 16.95 ATOM 2417 CE2 TYR A 315−0.552 23.261 −22.423 1.00 15.41 ATOM 2418 CD2 TYR A 315 −0.492 23.539−21.044 1.00 14.48 ATOM 2419 C TYR A 315 0.489 26.777 −19.107 1.00 15.56ATOM 2420 O TYR A 315 −0.688 26.888 −18.748 1.00 16.36 ATOM 2421 N TYR A316 1.072 27.645 −19.944 1.00 16.61 ATOM 2422 CA TYR A 316 0.404 28.890−20.380 1.00 17.53 ATOM 2423 CB TYR A 316 −0.778 28.603 −21.337 1.0018.31 ATOM 2424 CG TYR A 316 −0.329 28.321 −22.742 1.00 19.74 ATOM 2425CD1 TYR A 316 −0.071 27.026 −23.169 1.00 18.95 ATOM 2426 CE1 TYR A 3160.353 26.757 −24.466 1.00 18.69 ATOM 2427 CZ TYR A 316 0.551 27.812−25.342 1.00 21.77 ATOM 2428 OH TYR A 316 1.002 27.557 −26.617 1.0023.75 ATOM 2429 CE2 TYR A 316 0.329 29.125 −24.932 1.00 22.39 ATOM 2430CD2 TYR A 316 −0.111 29.369 −23.639 1.00 21.90 ATOM 2431 C TYR A 316−0.037 29.730 −19.173 1.00 17.87 ATOM 2432 O TYR A 316 −0.966 30.517−19.266 1.00 17.06 ATOM 2433 N ASN A 317 0.689 29.555 −18.066 1.00 18.34ATOM 2434 CA ASN A 317 0.483 30.231 −16.766 1.00 19.27 ATOM 2435 CB ASNA 317 0.106 31.699 −16.921 1.00 20.01 ATOM 2436 CG ASN A 317 1.17132.489 −17.624 1.00 24.51 ATOM 2437 OD1 ASN A 317 2.363 32.384 −17.3051.00 29.46 ATOM 2438 ND2 ASN A 317 0.756 33.269 −18.603 1.00 29.08 ATOM2439 C ASN A 317 −0.506 29.551 −15.842 1.00 18.28 ATOM 2440 O ASN A 317−0.706 30.001 −14.719 1.00 19.05 ATOM 2441 N GLY A 318 −1.114 28.459−16.300 1.00 17.74 ATOM 2442 CA GLY A 318 −2.086 27.721 −15.475 1.0015.34 ATOM 2443 C GLY A 318 −3.458 28.356 −15.550 1.00 15.47 ATOM 2444 OGLY A 318 −3.700 29.390 −14.932 1.00 15.75 ATOM 2445 N ASN A 319 −4.36927.733 −16.306 1.00 13.16 ATOM 2446 CA ASN A 319 −5.672 28.305 −16.5571.00 12.74 ATOM 2447 CB ASN A 319 −5.693 28.883 −17.980 1.00 12.31 ATOM2448 CG ASN A 319 −4.676 29.979 −18.187 1.00 13.01 ATOM 2449 OD1 ASN A319 −4.832 31.117 −17.699 1.00 14.18 ATOM 2450 ND2 ASN A 319 −3.64029.665 −18.942 1.00 11.49 ATOM 2451 C ASN A 319 −6.799 27.271 −16.4421.00 12.27 ATOM 2452 O ASN A 319 −6.545 26.071 −16.456 1.00 12.28 ATOM2453 N PRO A 320 −8.054 27.732 −16.334 1.00 12.96 ATOM 2454 CA PRO A 320−9.113 26.759 −16.472 1.00 12.58 ATOM 2455 CB PRO A 320 −10.395 27.579−16.324 1.00 13.28 ATOM 2456 CG PRO A 320 −10.007 29.011 −16.183 1.0014.34 ATOM 2457 CD PRO A 320 −8.537 29.090 −15.991 1.00 12.66 ATOM 2458C PRO A 320 −9.101 26.090 −17.851 1.00 12.18 ATOM 2459 O PRO A 320−8.643 26.698 −18.820 1.00 11.99 ATOM 2460 N TRP A 321 −9.589 24.852−17.912 1.00 11.79 ATOM 2461 CA TRP A 321 −9.739 24.116 −19.154 1.0011.97 ATOM 2462 CB TRP A 321 −8.988 22.775 −19.063 1.00 11.15 ATOM 2463CG TRP A 321 −7.469 22.900 −19.200 1.00 12.16 ATOM 2464 CD1 TRP A 321−6.658 23.837 −18.627 1.00 13.28 ATOM 2465 NE1 TRP A 321 −5.347 23.636−19.016 1.00 13.24 ATOM 2466 CE2 TRP A 321 −5.290 22.538 −19.831 1.0013.51 ATOM 2467 CD2 TRP A 321 −6.617 22.054 −19.978 1.00 12.68 ATOM 2468CE3 TRP A 321 −6.846 20.938 −20.787 1.00 14.41 ATOM 2469 CZ3 TRP A 321−5.741 20.323 −21.428 1.00 13.49 ATOM 2470 CH2 TRP A 321 −4.436 20.819−21.250 1.00 13.43 ATOM 2471 CZ2 TRP A 321 −4.193 21.548 −20.479 1.0014.69 ATOM 2472 C TRP A 321 −11.202 23.797 −19.342 1.00 11.99 ATOM 2473O TRP A 321 −11.875 23.448 −18.388 1.00 11.51 ATOM 2474 N TYR A 322−11.696 23.896 −20.579 1.00 11.47 ATOM 2475 CA TYR A 322 −13.088 23.511−20.841 1.00 11.31 ATOM 2476 CB TYR A 322 −13.433 23.691 −22.322 1.0012.14 ATOM 2477 CG TYR A 322 −13.352 25.130 −22.793 1.00 12.81 ATOM 2478CD1 TYR A 322 −12.260 25.574 −23.509 1.00 11.43 ATOM 2479 CE1 TYR A 322−12.173 26.914 −23.965 1.00 12.91 ATOM 2480 CZ TYR A 322 −13.216 27.802−23.697 1.00 14.27 ATOM 2481 OH TYR A 322 −13.127 29.104 −24.146 1.0015.10 ATOM 2482 CE2 TYR A 322 −14.324 27.373 −22.982 1.00 13.40 ATOM2483 CD2 TYR A 322 −14.378 26.031 −22.522 1.00 11.58 ATOM 2484 C TYR A322 −13.367 22.082 −20.433 1.00 11.31 ATOM 2485 O TYR A 322 −14.38021.795 −19.771 1.00 11.08 ATOM 2486 N LEU A 323 −12.480 21.169 −20.8141.00 10.96 ATOM 2487 CA LEU A 323 −12.770 19.750 −20.561 1.00 11.04 ATOM2488 CB LEU A 323 −11.787 18.844 −21.315 1.00 11.26 ATOM 2489 CG LEU A323 −10.314 18.876 −20.903 1.00 10.53 ATOM 2490 CD1 LEU A 323 −10.07417.902 −19.745 1.00 14.57 ATOM 2491 CD2 LEU A 323 −9.474 18.437 −22.1121.00 13.19 ATOM 2492 C LEU A 323 −12.778 19.449 −19.048 1.00 11.68 ATOM2493 O LEU A 323 −13.444 18.510 −18.602 1.00 12.06 ATOM 2494 N ALA A 324−12.036 20.239 −18.268 1.00 9.86 ATOM 2495 CA ALA A 324 −11.969 20.017−16.812 1.00 10.09 ATOM 2496 CB ALA A 324 −10.746 20.767 −16.234 1.009.76 ATOM 2497 C ALA A 324 −13.272 20.518 −16.178 1.00 10.17 ATOM 2498 OALA A 324 −13.866 19.840 −15.325 1.00 10.29 ATOM 2499 N THR A 325−13.758 21.662 −16.665 1.00 9.84 ATOM 2500 CA THR A 325 −15.000 22.267−16.172 1.00 11.14 ATOM 2501 CB THR A 325 −15.102 23.765 −16.623 1.0012.15 ATOM 2502 OG1 THR A 325 −14.002 24.498 −16.063 1.00 13.16 ATOM2503 CG2 THR A 325 −16.402 24.411 −16.152 1.00 11.83 ATOM 2504 C THR A325 −16.218 21.413 −16.570 1.00 11.50 ATOM 2505 O THR A 325 −17.08621.126 −15.727 1.00 10.79 ATOM 2506 N PHE A 326 −16.234 20.925 −17.8161.00 10.79 ATOM 2507 CA PHE A 326 −17.272 19.959 −18.240 1.00 12.12 ATOM2508 CB PHE A 326 −17.194 19.652 −19.746 1.00 12.14 ATOM 2509 CG PHE A326 −17.518 20.851 −20.640 1.00 13.71 ATOM 2510 CD1 PHE A 326 −16.77721.077 −21.804 1.00 15.21 ATOM 2511 CE1 PHE A 326 −17.043 22.188 −22.6351.00 14.99 ATOM 2512 CZ PHE A 326 −18.072 23.066 −22.311 1.00 16.33 ATOM2513 CE2 PHE A 326 −18.851 22.832 −21.160 1.00 20.12 ATOM 2514 CD2 PHE A326 −18.561 21.717 −20.331 1.00 16.63 ATOM 2515 C PHE A 326 −17.21618.643 −17.464 1.00 11.56 ATOM 2516 O PHE A 326 −18.263 18.069 −17.1801.00 11.74 ATOM 2517 N ALA A 327 −16.014 18.174 −17.103 1.00 11.35 ATOM2518 CA ALA A 327 −15.889 16.909 −16.346 1.00 11.41 ATOM 2519 CB ALA A327 −14.397 16.538 −16.158 1.00 11.95 ATOM 2520 C ALA A 327 −16.61216.964 −14.965 1.00 12.04 ATOM 2521 O ALA A 327 −17.260 15.985 −14.5611.00 12.69 ATOM 2522 N ALA A 328 −16.505 18.097 −14.266 1.00 12.13 ATOM2523 CA ALA A 328 −17.207 18.293 −12.985 1.00 12.24 ATOM 2524 CB ALA A328 −16.871 19.662 −12.369 1.00 12.48 ATOM 2525 C ALA A 328 −18.70718.157 −13.177 1.00 12.90 ATOM 2526 O ALA A 328 −19.378 17.454 −12.4111.00 13.60 ATOM 2527 N ALA A 329 −19.239 18.814 −14.202 1.00 12.55 ATOM2528 CA ALA A 329 −20.669 18.682 −14.504 1.00 12.31 ATOM 2529 CB ALA A329 −21.027 19.551 −15.692 1.00 12.87 ATOM 2530 C ALA A 329 −21.03517.226 −14.788 1.00 12.71 ATOM 2531 O ALA A 329 −22.016 16.700 −14.2661.00 12.32 ATOM 2532 N GLU A 330 −20.231 16.572 −15.629 1.00 12.54 ATOM2533 CA GLU A 330 −20.500 15.187 −16.003 1.00 12.84 ATOM 2534 CB GLU A330 −19.519 14.718 −17.100 1.00 12.55 ATOM 2535 CG GLU A 330 −19.85013.303 −17.626 1.00 13.80 ATOM 2536 CD GLU A 330 −19.108 12.953 −18.9171.00 13.54 ATOM 2537 OE1 GLU A 330 −18.650 13.889 −19.604 1.00 12.29ATOM 2538 OE2 GLU A 330 −18.998 11.739 −19.209 1.00 14.52 ATOM 2539 CGLU A 330 −20.523 14.231 −14.809 1.00 12.94 ATOM 2540 O GLU A 330−21.400 13.346 −14.726 1.00 12.90 ATOM 2541 N GLN A 331 −19.598 14.402−13.866 1.00 12.03 ATOM 2542 CA GLN A 331 −19.589 13.502 −12.726 1.0012.38 ATOM 2543 CB GLN A 331 −18.415 13.795 −11.797 1.00 12.24 ATOM 2544CG GLN A 331 −18.357 12.759 −10.670 1.00 13.61 ATOM 2545 CD GLN A 331−17.327 13.072 −9.608 1.00 15.82 ATOM 2546 OE1 GLN A 331 −16.263 13.617−9.895 1.00 15.39 ATOM 2547 NE2 GLN A 331 −17.628 12.702 −8.372 1.0013.76 ATOM 2548 C GLN A 331 −20.912 13.643 −11.969 1.00 12.33 ATOM 2549O GLN A 331 −21.512 12.659 −11.556 1.00 12.45 ATOM 2550 N LEU A 332−21.377 14.873 −11.844 1.00 12.57 ATOM 2551 CA LEU A 332 −22.628 15.138−11.134 1.00 13.59 ATOM 2552 CB LEU A 332 −22.747 16.631 −10.868 1.0013.17 ATOM 2553 CG LEU A 332 −21.681 17.142 −9.867 1.00 16.56 ATOM 2554CD1 LEU A 332 −21.718 18.678 −9.801 1.00 18.10 ATOM 2555 CD2 LEU A 332−21.851 16.476 −8.492 1.00 19.47 ATOM 2556 C LEU A 332 −23.861 14.600−11.864 1.00 13.57 ATOM 2557 O LEU A 332 −24.770 14.053 −11.239 1.0013.24 ATOM 2558 N TYR A 333 −23.909 14.766 −13.179 1.00 13.90 ATOM 2559CA TYR A 333 −24.988 14.131 −13.972 1.00 14.37 ATOM 2560 CB TYR A 333−24.901 14.523 −15.468 1.00 14.48 ATOM 2561 CG TYR A 333 −25.056 16.001−15.721 1.00 13.91 ATOM 2562 CD1 TYR A 333 −26.086 16.738 −15.118 1.0014.64 ATOM 2563 CE1 TYR A 333 −26.208 18.117 −15.350 1.00 15.65 ATOM2564 CZ TYR A 333 −25.315 18.758 −16.196 1.00 16.47 ATOM 2565 OH TYR A333 −25.431 20.101 −16.442 1.00 17.22 ATOM 2566 CE2 TYR A 333 −24.31018.050 −16.836 1.00 16.59 ATOM 2567 CD2 TYR A 333 −24.192 16.669 −16.6011.00 11.27 ATOM 2568 C TYR A 333 −25.022 12.613 −13.843 1.00 15.03 ATOM2569 O TYR A 333 −26.108 12.012 −13.824 1.00 14.78 ATOM 2570 N ASP A 334−23.836 11.998 −13.807 1.00 14.06 ATOM 2571 CA ASP A 334 −23.714 10.555−13.602 1.00 14.83 ATOM 2572 CB ASP A 334 −22.239 10.114 −13.714 1.0013.83 ATOM 2573 CG ASP A 334 −21.708 10.149 −15.136 1.00 15.84 ATOM 2574OD1 ASP A 334 −22.495 10.373 −16.081 1.00 13.95 ATOM 2575 OD2 ASP A 334−20.470 9.943 −15.313 1.00 15.50 ATOM 2576 C ASP A 334 −24.254 10.163−12.224 1.00 15.21 ATOM 2577 O ASP A 334 −24.941 9.132 −12.080 1.0015.93 ATOM 2578 N ALA A 335 −23.933 10.969 −11.213 1.00 15.09 ATOM 2579CA ALA A 335 −24.454 10.735 −9.855 1.00 16.00 ATOM 2580 CB ALA A 335−23.809 11.719 −8.864 1.00 15.13 ATOM 2581 C ALA A 335 −25.980 10.823−9.803 1.00 16.10 ATOM 2582 O ALA A 335 −26.643 9.916 −9.245 1.00 16.77ATOM 2583 N ILE A 336 −26.530 11.879 −10.398 1.00 16.35 ATOM 2584 CA ILEA 336 −27.987 12.087 −10.470 1.00 18.39 ATOM 2585 CB ILE A 336 −28.33213.422 −11.162 1.00 18.85 ATOM 2586 CG1 ILE A 336 −27.891 14.596 −10.2791.00 19.14 ATOM 2587 CD1 ILE A 336 −27.879 15.904 −10.986 1.00 22.50ATOM 2588 CG2 ILE A 336 −29.839 13.539 −11.506 1.00 20.14 ATOM 2589 CILE A 336 −28.681 10.902 −11.156 1.00 18.83 ATOM 2590 O ILE A 336−29.707 10.404 −10.675 1.00 18.06 ATOM 2591 N TYR A 337 −28.102 10.443−12.267 1.00 18.50 ATOM 2592 CA TYR A 337 −28.642 9.287 −12.970 1.0018.99 ATOM 2593 CB TYR A 337 −27.753 8.908 −14.169 1.00 19.80 ATOM 2594CG TYR A 337 −28.328 7.737 −14.954 1.00 20.76 ATOM 2595 CD1 TYR A 337−27.988 6.429 −14.620 1.00 20.95 ATOM 2596 CE1 TYR A 337 −28.511 5.345−15.322 1.00 22.94 ATOM 2597 CZ TYR A 337 −29.382 5.559 −16.356 1.0022.19 ATOM 2598 OH TYR A 337 −29.877 4.447 −17.018 1.00 24.87 ATOM 2599CE2 TYR A 337 −29.752 6.845 −16.721 1.00 22.31 ATOM 2600 CD2 TYR A 337−29.220 7.942 −16.009 1.00 21.58 ATOM 2601 C TYR A 337 −28.839 8.083−12.057 1.00 18.60 ATOM 2602 O TYR A 337 −29.918 7.476 −12.041 1.0018.61 ATOM 2603 N VAL A 338 −27.802 7.737 −11.297 1.00 18.67 ATOM 2604CA VAL A 338 −27.837 6.573 −10.406 1.00 18.90 ATOM 2605 CB VAL A 338−26.424 6.195 −9.919 1.00 18.99 ATOM 2606 CG1 VAL A 338 −26.462 5.121−8.820 1.00 19.71 ATOM 2607 CG2 VAL A 338 −25.600 5.698 −11.111 1.0018.75 ATOM 2608 C VAL A 338 −28.810 6.788 −9.234 1.00 19.41 ATOM 2609 OVAL A 338 −29.565 5.871 −8.869 1.00 19.45 ATOM 2610 N TRP A 339 −28.7977.987 −8.654 1.00 19.81 ATOM 2611 CA TRP A 339 −29.743 8.290 −7.559 1.0020.46 ATOM 2612 CB TRP A 339 −29.514 9.705 −7.029 1.00 20.35 ATOM 2613CG TRP A 339 −28.222 9.830 −6.329 1.00 18.64 ATOM 2614 CD1 TRP A 339−27.540 8.846 −5.676 1.00 16.51 ATOM 2615 NE1 TRP A 339 −26.391 9.359−5.126 1.00 17.81 ATOM 2616 CE2 TRP A 339 −26.312 10.693 −5.423 1.0017.12 ATOM 2617 CD2 TRP A 339 −27.452 11.025 −6.183 1.00 17.64 ATOM 2618CE3 TRP A 339 −27.624 12.343 −6.614 1.00 17.59 ATOM 2619 CZ3 TRP A 339−26.637 13.283 −6.284 1.00 19.24 ATOM 2620 CH2 TRP A 339 −25.510 12.912−5.520 1.00 18.24 ATOM 2621 CZ2 TRP A 339 −25.320 11.626 −5.103 1.0018.45 ATOM 2622 C TRP A 339 −31.201 8.108 −7.997 1.00 21.83 ATOM 2623 OTRP A 339 −31.981 7.478 −7.274 1.00 22.01 ATOM 2624 N LYS A 340 −31.5498.646 −9.168 1.00 22.85 ATOM 2625 CA LYS A 340 −32.904 8.541 −9.721 1.0025.61 ATOM 2626 CB LYS A 340 −33.066 9.411 −10.967 1.00 25.52 ATOM 2627CG LYS A 340 −33.174 10.905 −10.689 1.00 28.19 ATOM 2628 CD LYS A 340−33.227 11.692 −11.991 1.00 34.04 ATOM 2629 CE LYS A 340 −33.966 13.011−11.805 1.00 38.04 ATOM 2630 NZ LYS A 340 −33.868 13.876 −13.017 1.0041.83 ATOM 2631 C LYS A 340 −33.276 7.108 −10.062 1.00 27.14 ATOM 2632 OLYS A 340 −34.413 6.686 −9.830 1.00 27.56 ATOM 2633 N LYS A 341 −32.3176.358 −10.604 1.00 28.13 ATOM 2634 CA LYS A 341 −32.552 4.975 −11.0181.00 30.18 ATOM 2635 CB LYS A 341 −31.358 4.428 −11.800 1.00 29.83 ATOM2636 CG LYS A 341 −31.688 3.173 −12.624 1.00 33.04 ATOM 2637 CD LYS A341 −30.472 2.624 −13.395 1.00 33.62 ATOM 2638 CE LYS A 341 −29.6521.592 −12.588 1.00 38.22 ATOM 2639 NZ LYS A 341 −28.691 2.188 −11.5731.00 40.88 ATOM 2640 C LYS A 341 −32.816 4.081 −9.817 1.00 30.19 ATOM2641 O LYS A 341 −33.744 3.260 −9.837 1.00 30.15 ATOM 2642 N THR A 342−31.999 4.246 −8.777 1.00 29.52 ATOM 2643 CA THR A 342 −32.074 3.400−7.595 1.00 29.75 ATOM 2644 CB THR A 342 −30.687 3.221 −6.916 1.00 29.68ATOM 2645 OG1 THR A 342 −30.254 4.458 −6.333 1.00 32.01 ATOM 2646 CG2THR A 342 −29.628 2.735 −7.929 1.00 31.40 ATOM 2647 C THR A 342 −33.1293.901 −6.596 1.00 29.01 ATOM 2648 O THR A 342 −33.572 3.148 −5.734 1.0029.92 ATOM 2649 N GLY A 343 −33.534 5.158 −6.732 1.00 28.20 ATOM 2650 CAGLY A 343 −34.537 5.782 −5.862 1.00 28.30 ATOM 2651 C GLY A 343 −34.0686.045 −4.438 1.00 27.91 ATOM 2652 O GLY A 343 −34.887 6.133 −3.519 1.0028.16 ATOM 2653 N SER A 344 −32.760 6.226 −4.260 1.00 27.22 ATOM 2654 CASER A 344 −32.142 6.306 −2.939 1.00 26.60 ATOM 2655 CB SER A 344 −31.8704.880 −2.462 1.00 27.28 ATOM 2656 OG SER A 344 −31.354 4.855 −1.161 1.0029.50 ATOM 2657 C SER A 344 −30.823 7.107 −2.979 1.00 26.02 ATOM 2658 OSER A 344 −30.068 6.992 −3.944 1.00 25.80 ATOM 2659 N ILE A 345 −30.5577.900 −1.936 1.00 24.20 ATOM 2660 CA ILE A 345 −29.295 8.641 −1.770 1.0023.04 ATOM 2661 CB ILE A 345 −29.477 10.171 −1.954 1.00 23.03 ATOM 2662CG1 ILE A 345 −30.021 10.474 −3.340 1.00 22.44 ATOM 2663 CD1 ILE A 345−30.399 11.918 −3.599 1.00 23.24 ATOM 2664 CG2 ILE A 345 −28.138 10.918−1.670 1.00 22.00 ATOM 2665 C ILE A 345 −28.726 8.415 −0.378 1.00 23.13ATOM 2666 O ILE A 345 −29.392 8.684 0.623 1.00 23.57 ATOM 2667 N THR A346 −27.490 7.943 −0.307 1.00 22.23 ATOM 2668 CA THR A 346 −26.820 7.7650.963 1.00 23.25 ATOM 2669 CB THR A 346 −26.246 6.338 1.101 1.00 23.78ATOM 2670 OG1 THR A 346 −27.327 5.396 1.020 1.00 27.42 ATOM 2671 CG2 THRA 346 −25.507 6.129 2.443 1.00 24.74 ATOM 2672 C THR A 346 −25.753 8.8491.138 1.00 23.03 ATOM 2673 O THR A 346 −24.916 9.067 0.260 1.00 23.47ATOM 2674 N VAL A 347 −25.848 9.561 2.255 1.00 21.33 ATOM 2675 CA VAL A347 −24.845 10.537 2.674 1.00 20.11 ATOM 2676 CB VAL A 347 −25.52211.844 3.212 1.00 19.06 ATOM 2677 CG1 VAL A 347 −24.489 12.834 3.7001.00 19.66 ATOM 2678 CG2 VAL A 347 −26.418 12.465 2.137 1.00 20.32 ATOM2679 C VAL A 347 −24.066 9.865 3.785 1.00 20.14 ATOM 2680 O VAL A 347−24.667 9.340 4.728 1.00 19.79 ATOM 2681 N THR A 348 −22.734 9.878 3.6711.00 19.85 ATOM 2682 CA THR A 348 −21.851 9.274 4.660 1.00 19.92 ATOM2683 CB THR A 348 −20.965 8.185 4.018 1.00 19.82 ATOM 2684 OG1 THR A 348−19.921 8.815 3.277 1.00 20.35 ATOM 2685 CG2 THR A 348 −21.785 7.2783.092 1.00 21.67 ATOM 2686 C THR A 348 −20.964 10.354 5.256 1.00 19.60ATOM 2687 O THR A 348 −20.961 11.484 4.760 1.00 19.51 ATOM 2688 N ALA A349 −20.191 10.006 6.292 1.00 19.18 ATOM 2689 CA ALA A 349 −19.24310.932 6.885 1.00 20.02 ATOM 2690 CB ALA A 349 −18.494 10.275 8.044 1.0020.61 ATOM 2691 C ALA A 349 −18.240 11.466 5.842 1.00 19.79 ATOM 2692 OALA A 349 −17.756 12.601 5.947 1.00 20.15 ATOM 2693 N THR A 350 −17.90610.619 4.873 1.00 18.87 ATOM 2694 CA THR A 350 −16.911 10.971 3.850 1.0018.30 ATOM 2695 CB THR A 350 −16.435 9.717 3.093 1.00 18.67 ATOM 2696OG1 THR A 350 −15.780 8.850 4.027 1.00 19.82 ATOM 2697 CG2 THR A 350−15.426 10.097 1.974 1.00 17.73 ATOM 2698 C THR A 350 −17.463 12.0032.871 1.00 17.30 ATOM 2699 O THR A 350 −16.747 12.930 2.487 1.00 17.99ATOM 2700 N SER A 351 −18.716 11.847 2.467 1.00 16.16 ATOM 2701 CA SER A351 −19.316 12.803 1.517 1.00 15.78 ATOM 2702 CB SER A 351 −20.21412.076 0.512 1.00 15.85 ATOM 2703 OG SER A 351 −21.280 11.412 1.156 1.0017.14 ATOM 2704 C SER A 351 −20.087 13.941 2.193 1.00 15.63 ATOM 2705 OSER A 351 −20.736 14.743 1.524 1.00 13.62 ATOM 2706 N LEU A 352 −20.04814.006 3.527 1.00 15.09 ATOM 2707 CA LEU A 352 −20.901 14.985 4.212 1.0016.29 ATOM 2708 CB LEU A 352 −20.759 14.851 5.736 1.00 16.64 ATOM 2709CG LEU A 352 −21.713 15.734 6.570 1.00 17.22 ATOM 2710 CD1 LEU A 352−23.138 15.281 6.418 1.00 19.06 ATOM 2711 CD2 LEU A 352 −21.263 15.6368.032 1.00 20.02 ATOM 2712 C LEU A 352 −20.592 16.427 3.787 1.00 16.09ATOM 2713 O LEU A 352 −21.499 17.219 3.601 1.00 16.35 ATOM 2714 N ALA A353 −19.311 16.763 3.643 1.00 16.19 ATOM 2715 CA ALA A 353 −18.93318.148 3.354 1.00 15.74 ATOM 2716 CB ALA A 353 −17.460 18.314 3.424 1.0016.30 ATOM 2717 C ALA A 353 −19.459 18.544 1.972 1.00 16.11 ATOM 2718 OALA A 353 −19.957 19.668 1.781 1.00 15.44 ATOM 2719 N PHE A 354 −19.36717.607 1.021 1.00 16.10 ATOM 2720 CA PHE A 354 −19.885 17.849 −0.3251.00 15.25 ATOM 2721 CB PHE A 354 −19.718 16.618 −1.220 1.00 16.59 ATOM2722 CG PHE A 354 −20.497 16.707 −2.500 1.00 15.45 ATOM 2723 CD1 PHE A354 −19.959 17.375 −3.603 1.00 16.95 ATOM 2724 CE1 PHE A 354 −20.66417.489 −4.793 1.00 17.06 ATOM 2725 CZ PHE A 354 −21.956 16.953 −4.8881.00 16.75 ATOM 2726 CE2 PHE A 354 −22.517 16.276 −3.791 1.00 16.91 ATOM2727 CD2 PHE A 354 −21.778 16.160 −2.594 1.00 17.48 ATOM 2728 C PHE A354 −21.374 18.188 −0.226 1.00 15.56 ATOM 2729 O PHE A 354 −21.81519.183 −0.797 1.00 15.08 ATOM 2730 N PHE A 355 −22.140 17.347 0.474 1.0014.54 ATOM 2731 CA PHE A 355 −23.588 17.544 0.517 1.00 15.29 ATOM 2732CB PHE A 355 −24.295 16.319 1.078 1.00 15.61 ATOM 2733 CG PHE A 355−24.386 15.176 0.112 1.00 15.51 ATOM 2734 CD1 PHE A 355 −25.306 15.205−0.945 1.00 14.91 ATOM 2735 CE1 PHE A 355 −25.404 14.131 −1.832 1.0016.52 ATOM 2736 CZ PHE A 355 −24.567 13.033 −1.676 1.00 16.12 ATOM 2737CE2 PHE A 355 −23.648 12.994 −0.628 1.00 15.62 ATOM 2738 CD2 PHE A 355−23.562 14.071 0.255 1.00 13.62 ATOM 2739 C PHE A 355 −23.988 18.7891.303 1.00 15.19 ATOM 2740 O PHE A 355 −24.920 19.477 0.902 1.00 15.69ATOM 2741 N GLN A 356 −23.283 19.084 2.398 1.00 15.78 ATOM 2742 CA GLN A356 −23.679 20.216 3.257 1.00 16.16 ATOM 2743 CB GLN A 356 −22.98720.165 4.627 1.00 16.84 ATOM 2744 CG GLN A 356 −23.564 19.115 5.579 1.0017.13 ATOM 2745 CD GLN A 356 −22.907 19.170 6.973 1.00 18.06 ATOM 2746OE1 GLN A 356 −21.808 19.707 7.138 1.00 20.29 ATOM 2747 NE2 GLN A 356−23.569 18.589 7.965 1.00 20.95 ATOM 2748 C GLN A 356 −23.444 21.5462.584 1.00 16.08 ATOM 2749 O GLN A 356 −24.142 22.507 2.868 1.00 15.59ATOM 2750 N GLU A 357 −22.482 21.599 1.661 1.00 16.07 ATOM 2751 CA GLU A357 −22.261 22.808 0.884 1.00 16.41 ATOM 2752 CB GLU A 357 −20.99422.683 0.005 1.00 16.33 ATOM 2753 CG GLU A 357 −20.671 23.942 −0.7701.00 15.64 ATOM 2754 CD GLU A 357 −19.326 23.894 −1.516 1.00 17.67 ATOM2755 OE1 GLU A 357 −18.931 24.947 −2.066 1.00 19.03 ATOM 2756 OE2 GLU A357 −18.685 22.822 −1.575 1.00 14.75 ATOM 2757 C GLU A 357 −23.49223.105 0.019 1.00 15.84 ATOM 2758 O GLU A 357 −23.786 24.237 −0.224 1.0018.07 ATOM 2759 N LEU A 358 −24.213 22.084 −0.420 1.00 14.72 ATOM 2760CA LEU A 358 −25.364 22.251 −1.310 1.00 15.75 ATOM 2761 CB LEU A 358−25.368 21.147 −2.369 1.00 16.49 ATOM 2762 CG LEU A 358 −24.057 21.100−3.168 1.00 16.81 ATOM 2763 CD1 LEU A 358 −24.087 19.977 −4.182 1.0019.73 ATOM 2764 CD2 LEU A 358 −23.775 22.465 −3.846 1.00 19.34 ATOM 2765C LEU A 358 −26.708 22.251 −0.582 1.00 15.36 ATOM 2766 O LEU A 358−27.656 22.911 −1.028 1.00 14.78 ATOM 2767 N VAL A 359 −26.786 21.5110.520 1.00 15.34 ATOM 2768 CA VAL A 359 −28.001 21.404 1.321 1.00 15.00ATOM 2769 CB VAL A 359 −28.691 20.006 1.154 1.00 15.90 ATOM 2770 CG1 VALA 359 −29.999 19.917 1.962 1.00 15.16 ATOM 2771 CG2 VAL A 359 −28.96719.685 −0.348 1.00 16.26 ATOM 2772 C VAL A 359 −27.531 21.624 2.775 1.0014.72 ATOM 2773 O VAL A 359 −27.192 20.653 3.500 1.00 14.22 ATOM 2774 NPRO A 360 −27.467 22.893 3.193 1.00 14.98 ATOM 2775 CA PRO A 360 −26.93723.179 4.539 1.00 15.45 ATOM 2776 CB PRO A 360 −27.150 24.700 4.700 1.0015.45 ATOM 2777 CG PRO A 360 −27.188 25.219 3.274 1.00 16.15 ATOM 2778CD PRO A 360 −27.854 24.127 2.471 1.00 14.54 ATOM 2779 C PRO A 360−27.692 22.385 5.611 1.00 15.31 ATOM 2780 O PRO A 360 −28.918 22.2625.555 1.00 15.07 ATOM 2781 N GLY A 361 −26.936 21.842 6.560 1.00 15.94ATOM 2782 CA GLY A 361 −27.512 21.143 7.709 1.00 16.53 ATOM 2783 C GLY A361 −27.870 19.680 7.488 1.00 17.03 ATOM 2784 O GLY A 361 −28.268 18.9978.429 1.00 17.68 ATOM 2785 N VAL A 362 −27.762 19.176 6.261 1.00 16.13ATOM 2786 CA VAL A 362 −28.163 17.769 6.037 1.00 16.72 ATOM 2787 CB VALA 362 −28.217 17.416 4.525 1.00 16.47 ATOM 2788 CG1 VAL A 362 −26.80817.311 3.947 1.00 16.75 ATOM 2789 CG2 VAL A 362 −29.054 16.142 4.2801.00 17.21 ATOM 2790 C VAL A 362 −27.208 16.849 6.811 1.00 17.24 ATOM2791 O VAL A 362 −26.044 17.187 7.006 1.00 17.07 ATOM 2792 N THR A 363−27.695 15.703 7.274 1.00 18.15 ATOM 2793 CA THR A 363 −26.821 14.7898.025 1.00 19.86 ATOM 2794 CB THR A 363 −27.388 14.459 9.405 1.00 20.59ATOM 2795 OG1 THR A 363 −28.634 13.776 9.217 1.00 22.85 ATOM 2796 CG2THR A 363 −27.610 15.742 10.182 1.00 22.71 ATOM 2797 C THR A 363 −26.66013.476 7.310 1.00 19.18 ATOM 2798 O THR A 363 −27.398 13.184 6.371 1.0018.87 ATOM 2799 N ALA A 364 −25.697 12.679 7.769 1.00 19.67 ATOM 2800 CAALA A 364 −25.495 11.342 7.222 1.00 20.19 ATOM 2801 CB ALA A 364 −24.36110.637 7.930 1.00 20.38 ATOM 2802 C ALA A 364 −26.783 10.541 7.343 1.0021.17 ATOM 2803 O ALA A 364 −27.551 10.720 8.293 1.00 21.92 ATOM 2804 NGLY A 365 −27.041 9.687 6.360 1.00 21.67 ATOM 2805 CA GLY A 365 −28.2078.823 6.371 1.00 22.35 ATOM 2806 C GLY A 365 −28.584 8.415 4.968 1.0023.66 ATOM 2807 O GLY A 365 −27.924 8.804 3.991 1.00 23.66 ATOM 2808 NTHR A 366 −29.639 7.615 4.862 1.00 23.70 ATOM 2809 CA THR A 366 −30.1487.183 3.582 1.00 24.56 ATOM 2810 CB THR A 366 −30.188 5.644 3.491 1.0025.67 ATOM 2811 OG1 THR A 366 −28.849 5.143 3.649 1.00 27.09 ATOM 2812CG2 THR A 366 −30.715 5.216 2.159 1.00 25.47 ATOM 2813 C THR A 366−31.520 7.769 3.344 1.00 25.15 ATOM 2814 O THR A 366 −32.427 7.612 4.1771.00 25.01 ATOM 2815 N TYR A 367 −31.668 8.447 2.210 1.00 24.20 ATOM2816 CA TYR A 367 −32.900 9.146 1.883 1.00 24.30 ATOM 2817 CB TYR A 367−32.616 10.648 1.701 1.00 23.51 ATOM 2818 CG TYR A 367 31.924 11.2382.907 1.00 22.68 ATOM 2819 CD1 TYR A 367 −32.639 11.506 4.078 1.00 21.99ATOM 2820 CE1 TYR A 367 −32.012 12.019 5.199 1.00 20.27 ATOM 2821 CZ TYRA 367 −30.650 12.263 5.176 1.00 22.67 ATOM 2822 OH TYR A 367 −30.03612.789 6.287 1.00 21.24 ATOM 2823 CE2 TYR A 367 −29.897 11.994 4.0231.00 20.71 ATOM 2824 CD2 TYR A 367 −30.541 11.479 2.904 1.00 20.37 ATOM2825 C TYR A 367 −33.531 8.542 0.641 1.00 25.39 ATOM 2826 O TYR A 367−32.900 8.456 −0.415 1.00 24.86 ATOM 2827 N SER A 368 −34.782 8.1090.758 1.00 25.82 ATOM 2828 CA SER A 368 −35.416 7.454 −0.374 1.00 27.29ATOM 2829 CB SER A 368 −36.339 6.332 0.107 1.00 27.90 ATOM 2830 OG SER A368 −37.519 6.895 0.634 1.00 30.69 ATOM 2831 C SER A 368 −36.171 8.466−1.218 1.00 27.68 ATOM 2832 O SER A 368 −36.361 9.612 −0.805 1.00 26.96ATOM 2833 N SER A 369 −36.629 8.025 −2.388 1.00 28.98 ATOM 2834 CA SER A369 −37.260 8.908 −3.367 1.00 30.52 ATOM 2835 CB SER A 369 −37.520 8.167−4.681 1.00 30.90 ATOM 2836 OG SER A 369 −38.269 6.983 −4.452 1.00 32.57ATOM 2837 C SER A 369 −38.536 9.583 −2.871 1.00 31.50 ATOM 2838 O SER A369 −38.954 10.572 −3.442 1.00 32.33 ATOM 2839 N SER A 370 −39.150 9.067−1.809 1.00 32.18 ATOM 2840 CA SER A 370 −40.365 9.712 −1.279 1.00 32.96ATOM 2841 CB SER A 370 −41.313 8.692 −0.624 1.00 33.18 ATOM 2842 OG SERA 370 −40.610 7.847 0.273 1.00 34.18 ATOM 2843 C SER A 370 −40.04910.864 −0.323 1.00 32.37 ATOM 2844 O SER A 370 −40.901 11.729 −0.0781.00 33.26 ATOM 2845 N SER A 371 −38.825 10.893 0.197 1.00 31.13 ATOM2846 CA SER A 371 −38.443 11.911 1.174 1.00 30.04 ATOM 2847 CB SER A 371−37.180 11.487 1.912 1.00 29.83 ATOM 2848 OG SER A 371 −36.046 11.7141.100 1.00 30.43 ATOM 2849 C SER A 371 −38.247 13.295 0.553 1.00 29.13ATOM 2850 O SER A 371 −37.795 13.424 −0.589 1.00 28.84 ATOM 2851 N SER A372 −38.571 14.340 1.312 1.00 27.84 ATOM 2852 CA SER A 372 −38.30015.689 0.845 1.00 27.18 ATOM 2853 CB SER A 372 −38.896 16.737 1.789 1.0027.36 ATOM 2854 OG SER A 372 −38.331 16.609 3.080 1.00 28.50 ATOM 2855 CSER A 372 −36.783 15.902 0.680 1.00 25.79 ATOM 2856 O SER A 372 −36.35816.690 −0.173 1.00 26.29 ATOM 2857 N THR A 373 −35.979 15.193 1.479 1.0024.06 ATOM 2858 CA THR A 373 −34.517 15.337 1.448 1.00 22.51 ATOM 2859CB THR A 373 −33.833 14.501 2.545 1.00 22.26 ATOM 2860 OG1 THR A 373−34.543 14.636 3.788 1.00 23.04 ATOM 2861 CG2 THR A 373 −32.370 14.9262.734 1.00 21.06 ATOM 2862 C THR A 373 −33.984 14.906 0.076 1.00 21.61ATOM 2863 O THR A 373 −33.134 15.578 −0.513 1.00 19.74 ATOM 2864 N PHE A374 −34.493 13.777 −0.413 1.00 21.13 ATOM 2865 CA PHE A 374 −34.13713.280 −1.749 1.00 22.10 ATOM 2866 CB PHE A 374 −34.950 12.023 −2.0511.00 22.12 ATOM 2867 CG PHE A 374 −34.624 11.380 −3.366 1.00 22.90 ATOM2868 CD1 PHE A 374 −33.677 10.368 −3.432 1.00 23.83 ATOM 2869 CE1 PHE A374 −33.381 9.749 −4.649 1.00 22.56 ATOM 2870 CZ PHE A 374 −34.04110.162 −5.802 1.00 23.24 ATOM 2871 CE2 PHE A 374 −34.985 11.161 −5.7521.00 23.36 ATOM 2872 CD2 PHE A 374 −35.280 11.769 −4.523 1.00 23.73 ATOM2873 C PHE A 374 −34.343 14.349 −2.818 1.00 22.24 ATOM 2874 O PHE A 374−33.413 14.681 −3.548 1.00 22.63 ATOM 2875 N THR A 375 −35.549 14.923−2.880 1.00 22.72 ATOM 2876 CA THR A 375 −35.890 15.963 −3.852 1.0023.34 ATOM 2877 CB THR A 375 −37.364 16.398 −3.683 1.00 23.63 ATOM 2878OG1 THR A 375 −38.193 15.244 −3.809 1.00 27.83 ATOM 2879 CG2 THR A 375−37.768 17.413 −4.749 1.00 27.05 ATOM 2880 C THR A 375 −35.003 17.203−3.746 1.00 22.66 ATOM 2881 O THR A 375 −34.603 17.766 −4.756 1.00 21.43ATOM 2882 N ASN A 376 −34.744 17.632 −2.508 1.00 20.80 ATOM 2883 CA ASNA 376 −33.880 18.766 −2.207 1.00 21.33 ATOM 2884 CB ASN A 376 −33.85618.975 −0.688 1.00 21.98 ATOM 2885 CG ASN A 376 −33.343 20.354 −0.2781.00 27.01 ATOM 2886 OD1 ASN A 376 −32.582 21.011 −1.004 1.00 31.72 ATOM2887 ND2 ASN A 376 −33.748 20.793 0.913 1.00 30.14 ATOM 2888 C ASN A 376−32.465 18.527 −2.733 1.00 19.80 ATOM 2889 O ASN A 376 −31.898 19.389−3.415 1.00 19.75 ATOM 2890 N ILE A 377 −31.915 17.354 −2.431 1.00 19.00ATOM 2891 CA ILE A 377 −30.586 16.983 −2.916 1.00 18.66 ATOM 2892 CB ILEA 377 −30.081 15.651 −2.319 1.00 18.56 ATOM 2893 CG1 ILE A 377 −29.83415.813 −0.800 1.00 18.42 ATOM 2894 CD1 ILE A 377 −29.634 14.481 −0.0281.00 19.35 ATOM 2895 CG2 ILE A 377 −28.787 15.233 −3.025 1.00 18.07 ATOM2896 C ILE A 377 −30.546 16.964 −4.451 1.00 18.87 ATOM 2897 O ILE A 377−29.655 17.575 −5.058 1.00 18.47 ATOM 2898 N ILE A 378 −31.513 16.293−5.068 1.00 18.45 ATOM 2899 CA ILE A 378 −31.556 16.216 −6.539 1.0019.78 ATOM 2900 CB ILE A 378 −32.738 15.359 −7.085 1.00 20.45 ATOM 2901CG1 ILE A 378 −32.593 13.891 −6.650 1.00 22.32 ATOM 2902 CD1 ILE A 378−31.414 13.145 −7.270 1.00 24.68 ATOM 2903 CG2 ILE A 378 −32.829 15.472−8.646 1.00 21.27 ATOM 2904 C ILE A 378 −31.561 17.588 −7.177 1.00 19.82ATOM 2905 O ILE A 378 −30.760 17.849 −8.101 1.00 19.62 ATOM 2906 N ASN A379 −32.441 18.470 −6.689 1.00 18.68 ATOM 2907 CA ASN A 379 −32.53119.820 −7.224 1.00 19.13 ATOM 2908 CB ASN A 379 −33.738 20.578 −6.6581.00 20.08 ATOM 2909 CG ASN A 379 −35.066 19.956 −7.087 1.00 25.11 ATOM2910 OD1 ASN A 379 −35.121 19.173 −8.044 1.00 29.37 ATOM 2911 ND2 ASN A379 −36.144 20.289 −6.369 1.00 29.08 ATOM 2912 C ASN A 379 −31.24120.604 −7.040 1.00 17.96 ATOM 2913 O ASN A 379 −30.774 21.273 −7.9811.00 17.85 ATOM 2914 N ALA A 380 −30.662 20.497 −5.841 1.00 15.93 ATOM2915 CA ALA A 380 −29.458 21.241 −5.509 1.00 16.08 ATOM 2916 CB ALA A380 −29.120 21.061 −4.033 1.00 16.14 ATOM 2917 C ALA A 380 −28.29920.783 −6.389 1.00 15.64 ATOM 2918 O ALA A 380 −27.566 21.607 −6.9381.00 16.56 ATOM 2919 N VAL A 381 −28.153 19.471 −6.519 1.00 15.22 ATOM2920 CA VAL A 381 −27.039 18.912 −7.302 1.00 15.77 ATOM 2921 CB VAL A381 −26.823 17.403 −6.999 1.00 15.61 ATOM 2922 CG1 VAL A 381 −25.74716.777 −7.940 1.00 14.83 ATOM 2923 CG2 VAL A 381 −26.386 17.234 −5.5511.00 14.84 ATOM 2924 C VAL A 381 −27.243 19.211 −8.794 1.00 16.08 ATOM2925 O VAL A 381 −26.281 19.508 −9.505 1.00 16.62 ATOM 2926 N SER A 382−28.482 19.112 −9.278 1.00 16.66 ATOM 2927 CA SER A 382 −28.772 19.453−10.690 1.00 18.67 ATOM 2928 CB SER A 382 −30.246 19.212 −11.043 1.0018.26 ATOM 2929 OG SER A 382 −30.538 17.855 −10.893 1.00 24.56 ATOM 2930C SER A 382 −28.434 20.894 −11.005 1.00 18.10 ATOM 2931 O SER A 382−27.815 21.183 −12.027 1.00 18.05 ATOM 2932 N THR A 383 −28.853 21.810−10.132 1.00 17.66 ATOM 2933 CA THR A 383 −28.521 23.216 −10.298 1.0017.72 ATOM 2934 CB THR A 383 −29.199 24.063 −9.180 1.00 18.48 ATOM 2935OG1 THR A 383 −30.606 23.985 −9.373 1.00 19.72 ATOM 2936 CG2 THR A 383−28.771 25.550 −9.227 1.00 19.59 ATOM 2937 C THR A 383 −27.017 23.470−10.314 1.00 17.09 ATOM 2938 O THR A 383 −26.524 24.286 −11.109 1.0017.00 ATOM 2939 N TYR A 384 −26.299 22.774 −9.435 1.00 15.62 ATOM 2940CA TYR A 384 −24.858 22.925 −9.312 1.00 15.37 ATOM 2941 CB TYR A 384−24.397 22.164 −8.068 1.00 15.00 ATOM 2942 CG TYR A 384 −22.958 22.345−7.630 1.00 15.08 ATOM 2943 CD1 TYR A 384 −22.361 23.601 −7.578 1.0015.83 ATOM 2944 CE1 TYR A 384 −21.049 23.752 −7.131 1.00 16.33 ATOM 2945CZ TYR A 384 −20.321 22.623 −6.737 1.00 16.13 ATOM 2946 OH TYR A 384−19.018 22.738 −6.302 1.00 16.22 ATOM 2947 CE2 TYR A 384 −20.890 21.386−6.778 1.00 13.72 ATOM 2948 CD2 TYR A 384 −22.203 21.242 −7.232 1.0014.72 ATOM 2949 C TYR A 384 −24.186 22.396 −10.590 1.00 15.13 ATOM 2950O TYR A 384 −23.319 23.065 −11.173 1.00 14.43 ATOM 2951 N ALA A 385−24.605 21.213 −11.033 1.00 15.02 ATOM 2952 CA ALA A 385 −24.045 20.639−12.263 1.00 15.60 ATOM 2953 CB ALA A 385 −24.634 19.295 −12.503 1.0015.85 ATOM 2954 C ALA A 385 −24.249 21.564 −13.477 1.00 16.15 ATOM 2955O ALA A 385 −23.292 21.857 −14.211 1.00 15.49 ATOM 2956 N ASP A 386−25.483 22.055 −13.660 1.00 15.57 ATOM 2957 CA ASP A 386 −25.782 23.058−14.694 1.00 16.09 ATOM 2958 CB ASP A 386 −27.279 23.433 −14.687 1.0015.88 ATOM 2959 CG ASP A 386 −28.158 22.379 −15.349 1.00 18.85 ATOM 2960OD1 ASP A 386 −27.672 21.307 −15.766 1.00 18.94 ATOM 2961 OD2 ASP A 386−29.365 22.624 −15.461 1.00 23.88 ATOM 2962 C ASP A 386 −24.938 24.322−14.526 1.00 15.81 ATOM 2963 O ASP A 386 −24.594 24.998 −15.501 1.0016.29 ATOM 2964 N GLY A 387 −24.591 24.640 −13.290 1.00 15.76 ATOM 2965CA GLY A 387 −23.735 25.787 −13.038 1.00 14.35 ATOM 2966 C GLY A 387−22.354 25.654 −13.663 1.00 14.35 ATOM 2967 O GLY A 387 −21.791 26.644−14.129 1.00 13.79 ATOM 2968 N PHE A 388 −21.771 24.453 −13.624 1.0014.30 ATOM 2969 CA PHE A 388 −20.479 24.217 −14.312 1.00 14.69 ATOM 2970CB PHE A 388 −19.912 22.824 −13.987 1.00 14.42 ATOM 2971 CG PHE A 388−19.359 22.730 −12.584 1.00 13.79 ATOM 2972 CD1 PHE A 388 −18.139 23.335−12.269 1.00 14.50 ATOM 2973 CE1 PHE A 388 −17.621 23.261 −10.947 1.0016.38 ATOM 2974 CZ PHE A 388 −18.377 22.627 −9.951 1.00 14.77 ATOM 2975CE2 PHE A 388 −19.604 22.045 −10.265 1.00 16.35 ATOM 2976 CD2 PHE A 388−20.088 22.100 −11.578 1.00 14.00 ATOM 2977 C PHE A 388 −20.601 24.428−15.821 1.00 15.31 ATOM 2978 O PHE A 388 −19.740 25.078 −16.440 1.0015.55 ATOM 2979 N LEU A 389 −21.669 23.913 −16.415 1.00 16.52 ATOM 2980CA LEU A 389 −21.889 24.159 −17.856 1.00 17.84 ATOM 2981 CB LEU A 389−23.137 23.431 −18.382 1.00 17.83 ATOM 2982 CG LEU A 389 −23.172 21.911−18.427 1.00 22.75 ATOM 2983 CD1 LEU A 389 −24.247 21.418 −19.401 1.0022.55 ATOM 2984 CD2 LEU A 389 −21.805 21.333 −18.806 1.00 24.63 ATOM2985 C LEU A 389 −22.013 25.634 −18.136 1.00 18.32 ATOM 2986 O LEU A 389−21.409 26.138 −19.091 1.00 19.50 ATOM 2987 N SER A 390 −22.775 26.341−17.295 1.00 18.55 ATOM 2988 CA SER A 390 −23.021 27.767 −17.469 1.0019.33 ATOM 2989 CB SER A 390 −24.090 28.246 −16.491 1.00 19.89 ATOM 2990OG SER A 390 −25.325 27.693 −16.891 1.00 24.07 ATOM 2991 C SER A 390−21.763 28.603 −17.323 1.00 19.51 ATOM 2992 O SER A 390 −21.575 29.585−18.055 1.00 19.69 ATOM 2993 N GLU A 391 −20.893 28.200 −16.399 1.0018.87 ATOM 2994 CA GLU A 391 −19.633 28.879 −16.220 1.00 19.59 ATOM 2995CB GLU A 391 −18.901 28.393 −14.952 1.00 20.02 ATOM 2996 CG GLU A 391−19.528 28.924 −13.668 1.00 23.54 ATOM 2997 CD GLU A 391 −19.590 30.448−13.634 1.00 26.61 ATOM 2998 OE1 GLU A 391 −18.609 31.102 −14.023 1.0028.42 ATOM 2999 OE2 GLU A 391 −20.637 30.994 −13.227 1.00 29.52 ATOM3000 C GLU A 391 −18.738 28.729 −17.457 1.00 19.12 ATOM 3001 O GLU A 391−18.123 29.709 −17.906 1.00 19.40 ATOM 3002 N ALA A 392 −18.654 27.516−17.991 1.00 18.81 ATOM 3003 CA ALA A 392 −17.861 27.304 −19.201 1.0019.72 ATOM 3004 CB ALA A 392 −17.758 25.815 −19.526 1.00 19.45 ATOM 3005C ALA A 392 −18.478 28.098 −20.363 1.00 19.59 ATOM 3006 O ALA A 392−17.764 28.724 −21.157 1.00 18.65 ATOM 3007 N ALA A 393 −19.808 28.117−20.425 1.00 20.40 ATOM 3008 CA ALA A 393 −20.526 28.820 −21.507 1.0021.27 ATOM 3009 CB ALA A 393 −22.035 28.524 −21.421 1.00 21.83 ATOM 3010C ALA A 393 −20.266 30.334 −21.574 1.00 21.79 ATOM 3011 O ALA A 393−20.283 30.920 −22.664 1.00 21.96 ATOM 3012 N LYS A 394 −19.976 30.971−20.435 1.00 21.37 ATOM 3013 CA LYS A 394 −19.626 32.383 −20.447 1.0022.02 ATOM 3014 CB LYS A 394 −19.289 32.916 −19.043 1.00 23.11 ATOM 3015CG LYS A 394 −20.411 32.980 −18.044 1.00 25.98 ATOM 3016 CD LYS A 394−19.782 33.341 −16.700 1.00 28.89 ATOM 3017 CB LYS A 394 −20.793 33.314−15.576 1.00 34.05 ATOM 3018 NZ LYS A 394 −20.097 33.674 −14.290 1.0033.96 ATOM 3019 C LYS A 394 −18.403 32.626 −21.310 1.00 21.55 ATOM 3020O LYS A 394 −18.188 33.742 −21.771 1.00 22.41 ATOM 3021 N TYR A 395−17.570 31.604 −21.488 1.00 19.98 ATOM 3022 CA TYR A 395 −16.287 31.824−22.132 1.00 19.46 ATOM 3023 CB TYR A 395 −15.137 31.464 −21.185 1.0020.82 ATOM 3024 CG TYR A 395 −15.291 32.165 −19.872 1.00 22.04 ATOM 3025CD1 TYR A 395 −15.644 31.450 −18.716 1.00 23.21 ATOM 3026 CE1 TYR A 395−15.806 32.097 −17.508 1.00 23.70 ATOM 3027 CZ TYR A 395 −15.661 33.473−17.460 1.00 23.93 ATOM 3028 OH TYR A 395 −15.828 34.143 −16.272 1.0026.14 ATOM 3029 CE2 TYR A 395 −15.327 34.202 −18.593 1.00 24.38 ATOM3030 CD2 TYR A 395 −15.157 33.548 −19.791 1.00 22.37 ATOM 3031 C TYR A395 −16.157 31.119 −23.451 1.00 19.22 ATOM 3032 O TYR A 395 −15.04530.940 −23.941 1.00 18.70 ATOM 3033 N VAL A 396 −17.299 30.718 −24.0181.00 18.16 ATOM 3034 CA VAL A 396 −17.331 30.135 −25.352 1.00 19.03 ATOM3035 CB VAL A 396 −18.396 29.025 −25.458 1.00 18.18 ATOM 3036 CG1 VAL A396 −18.469 28.465 −26.898 1.00 18.63 ATOM 3037 CG2 VAL A 396 −18.09427.915 −24.452 1.00 18.97 ATOM 3038 C VAL A 396 −17.654 31.288 −26.3081.00 19.65 ATOM 3039 O VAL A 396 −18.644 31.986 −26.098 1.00 19.66 ATOM3040 N PRO A 397 −16.810 31.507 −27.328 1.00 20.41 ATOM 3041 CA PRO A397 −17.016 32.626 −28.256 1.00 20.82 ATOM 3042 CB PRO A 397 −15.79432.561 −29.175 1.00 21.47 ATOM 3043 CG PRO A 397 −14.819 31.725 −28.4751.00 21.69 ATOM 3044 CD PRO A 397 −15.598 30.741 −27.661 1.00 19.70 ATOM3045 C PRO A 397 −18.280 32.434 −29.073 1.00 21.11 ATOM 3046 O PRO A 397−18.844 31.339 −29.088 1.00 19.88 ATOM 3047 N ALA A 398 −18.713 33.492−29.765 1.00 21.26 ATOM 3048 CA ALA A 398 −19.951 33.424 −30.559 1.0021.44 ATOM 3049 CB ALA A 398 −20.227 34.766 −31.230 1.00 22.38 ATOM 3050C ALA A 398 −19.971 32.297 −31.587 1.00 21.30 ATOM 3051 O ALA A 398−21.038 31.769 −31.901 1.00 22.15 ATOM 3052 N ASP A 399 −18.804 31.896−32.102 1.00 20.30 ATOM 3053 CA ASP A 399 −18.780 30.858 −33.133 1.0019.40 ATOM 3054 CB ASP A 399 −17.587 31.032 −34.071 1.00 19.42 ATOM 3055CG ASP A 399 −16.233 30.835 −33.381 1.00 21.84 ATOM 3056 OD1 ASP A 399−16.146 30.569 −32.159 1.00 20.91 ATOM 3057 OD2 ASP A 399 −15.229 30.950−34.104 1.00 24.62 ATOM 3058 C ASP A 399 −18.834 29.435 −32.579 1.0018.14 ATOM 3059 O ASP A 399 −18.802 28.465 −33.350 1.00 16.78 ATOM 3060N GLY A 400 −18.891 29.322 −31.245 1.00 16.82 ATOM 3061 CA GLY A 400−18.996 28.015 −30.607 1.00 15.41 ATOM 3062 C GLY A 400 −17.693 27.229−30.556 1.00 15.07 ATOM 3063 O GLY A 400 −17.704 26.041 −30.203 1.0015.23 ATOM 3064 N SER A 401 −16.572 27.861 −30.882 1.00 14.21 ATOM 3065CA SER A 401 −15.312 27.119 −30.893 1.00 14.76 ATOM 3066 CB SER A 401−14.241 27.840 −31.718 1.00 14.71 ATOM 3067 OG SER A 401 −14.059 29.160−31.257 1.00 16.86 ATOM 3068 C SER A 401 −14.815 26.866 −29.448 1.0014.38 ATOM 3069 O SER A 401 −14.992 27.717 −28.562 1.00 14.58 ATOM 3070N LEU A 402 −14.169 25.720 −29.249 1.00 13.54 ATOM 3071 CA LEU A 402−13.603 25.364 −27.968 1.00 13.21 ATOM 3072 CB LEU A 402 −14.271 24.080−27.450 1.00 13.42 ATOM 3073 CG LEU A 402 −15.776 24.192 −27.162 1.0014.06 ATOM 3074 CD1 LEU A 402 −16.289 22.834 −26.668 1.00 13.87 ATOM3075 CD2 LEU A 402 −15.997 25.264 −26.109 1.00 17.00 ATOM 3076 C LEU A402 −12.111 25.143 −28.109 1.00 12.99 ATOM 3077 O LEU A 402 −11.69524.166 −28.707 1.00 13.19 ATOM 3078 N ALA A 403 −11.320 26.070 −27.5781.00 13.02 ATOM 3079 CA ALA A 403 −9.884 25.870 −27.454 1.00 12.06 ATOM3080 CB ALA A 403 −9.194 27.226 −27.220 1.00 11.77 ATOM 3081 C ALA A 403−9.591 24.907 −26.300 1.00 12.81 ATOM 3082 O ALA A 403 −10.508 24.315−25.714 1.00 12.36 ATOM 3083 N GLU A 404 −8.308 24.772 −25.959 1.0011.39 ATOM 3084 CA GLU A 404 −7.918 23.922 −24.855 1.00 11.47 ATOM 3085CB GLU A 404 −6.412 23.689 −24.931 1.00 11.02 ATOM 3086 CG GLU A 404−5.865 22.723 −23.873 1.00 11.30 ATOM 3087 CD GLU A 404 −4.363 22.669−23.954 1.00 12.25 ATOM 3088 OE1 GLU A 404 −3.729 23.692 −23.622 1.0012.06 ATOM 3089 OE2 GLU A 404 −3.818 21.624 −24.390 1.00 12.60 ATOM 3090C GLU A 404 −8.246 24.635 −23.538 1.00 11.77 ATOM 3091 O GLU A 404−8.755 24.006 −22.590 1.00 11.08 ATOM 3092 N GLN A 405 −7.890 25.924−23.453 1.00 12.07 ATOM 3093 CA GLN A 405 −7.952 26.655 −22.196 1.0013.33 ATOM 3094 CB GLN A 405 −6.539 26.986 −21.678 1.00 13.24 ATOM 3095CG GLN A 405 −5.625 25.821 −21.553 1.00 15.96 ATOM 3096 CD GLN A 405−4.229 26.213 −21.051 1.00 14.97 ATOM 3097 OE1 GLN A 405 −4.068 27.130−20.236 1.00 15.09 ATOM 3098 NE2 GLN A 405 −3.236 25.475 −21.496 1.0015.87 ATOM 3099 C GLN A 405 −8.687 27.985 −22.356 1.00 13.51 ATOM 3100 OGLN A 405 −8.870 28.475 −23.489 1.00 13.74 ATOM 3101 N PHE A 406 −9.04128.587 −21.226 1.00 12.60 ATOM 3102 CA PHE A 406 −9.516 29.990 −21.2071.00 13.82 ATOM 3103 CB PHE A 406 −11.058 30.104 −21.232 1.00 13.56 ATOM3104 CG PHE A 406 −11.800 29.385 −20.123 1.00 15.20 ATOM 3105 CD1 PHE A406 −12.155 28.026 −20.242 1.00 16.33 ATOM 3106 CE1 PHE A 406 −12.87927.370 −19.239 1.00 16.80 ATOM 3107 CZ PHE A 406 −13.340 28.094 −18.1141.00 16.74 ATOM 3108 CE2 PHE A 406 −13.020 29.453 −17.993 1.00 15.37ATOM 3109 CD2 PHE A 406 −12.260 30.101 −19.000 1.00 17.56 ATOM 3110 CPHE A 406 −8.836 30.737 −20.078 1.00 13.80 ATOM 3111 O PHE A 406 −8.58730.151 −19.018 1.00 14.02 ATOM 3112 N ASP A 407 −8.481 31.997 −20.3211.00 14.98 ATOM 3113 CA ASP A 407 −7.547 32.726 −19.438 1.00 15.04 ATOM3114 CB ASP A 407 −7.237 34.115 −20.032 1.00 15.99 ATOM 3115 CG ASP A407 −6.159 34.829 −19.293 1.00 18.17 ATOM 3116 OD1 ASP A 407 −6.47435.508 −18.293 1.00 20.41 ATOM 3117 OD2 ASP A 407 −4.993 34.683 −19.6851.00 20.75 ATOM 3118 C ASP A 407 −8.100 32.829 −18.005 1.00 14.54 ATOM3119 O ASP A 407 −9.257 33.185 −17.800 1.00 15.12 ATOM 3120 N ARG A 408−7.248 32.548 −17.018 1.00 14.63 ATOM 3121 CA ARG A 408 −7.644 32.530−15.609 1.00 15.33 ATOM 3122 CB ARG A 408 −6.453 32.095 −14.753 1.0015.32 ATOM 3123 CG ARG A 408 −5.236 33.062 −14.828 1.00 14.48 ATOM 3124CD ARG A 408 −4.009 32.479 −14.122 1.00 16.22 ATOM 3125 NE ARG A 408−4.237 32.248 −12.695 1.00 15.55 ATOM 3126 CZ ARG A 408 −3.613 31.323−11.961 1.00 18.66 ATOM 3127 NH1 ARG A 408 −3.878 31.231 −10.658 1.0017.51 ATOM 3128 NH2 ARG A 408 −2.717 30.499 −12.511 1.00 17.12 ATOM 3129C ARG A 408 −8.167 33.886 −15.108 1.00 16.66 ATOM 3130 O ARG A 408−8.898 33.943 −14.110 1.00 16.82 ATOM 3131 N ASN A 409 −7.781 34.964−15.790 1.00 18.00 ATOM 3132 CA ASN A 409 −8.252 36.316 −15.421 1.0020.06 ATOM 3133 CB ASN A 409 −7.069 37.275 −15.355 1.00 20.32 ATOM 3134CG ASN A 409 −6.119 36.937 −14.224 1.00 21.65 ATOM 3135 OD1 ASN A 409−6.549 36.678 −13.111 1.00 24.42 ATOM 3136 ND2 ASN A 409 −4.830 36.914−14.516 1.00 23.96 ATOM 3137 C ASN A 409 −9.320 36.903 −16.336 1.0021.43 ATOM 3138 O ASN A 409 −10.272 37.524 −15.857 1.00 22.03 ATOM 3139N SER A 410 −9.152 36.724 −17.646 1.00 22.25 ATOM 3140 CA SER A 410−10.007 37.410 −18.624 1.00 22.76 ATOM 3141 CB SER A 410 −9.146 38.159−19.636 1.00 23.45 ATOM 3142 OG SER A 410 −8.470 37.260 −20.495 1.0023.38 ATOM 3143 C SER A 410 −10.971 36.472 −19.343 1.00 22.82 ATOM 3144O SER A 410 −11.898 36.925 −20.010 1.00 23.59 ATOM 3145 N GLY A 411−10.758 35.161 −19.238 1.00 21.64 ATOM 3146 CA GLY A 411 −11.668 34.221−19.877 1.00 20.39 ATOM 3147 C GLY A 411 −11.476 34.087 −21.379 1.0019.99 ATOM 3148 O GLY A 411 −12.223 33.368 −22.029 1.00 20.85 ATOM 3149N THR A 412 −10.478 34.750 −21.941 1.00 19.04 ATOM 3150 CA THR A 412−10.268 34.658 −23.383 1.00 20.25 ATOM 3151 CB THR A 412 −9.447 35.853−23.922 1.00 21.81 ATOM 3152 OG1 THR A 412 −8.187 35.900 −23.257 1.0026.24 ATOM 3153 CG2 THR A 412 −10.160 37.163 −23.631 1.00 23.82 ATOM3154 C THR A 412 −9.615 33.294 −23.732 1.00 19.17 ATOM 3155 O THR A 412−8.786 32.796 −22.970 1.00 17.70 ATOM 3156 N PRO A 413 −9.996 32.688−24.874 1.00 18.84 ATOM 3157 CA PRO A 413 −9.466 31.348 −25.234 1.0018.32 ATOM 3158 CB PRO A 413 −10.220 31.002 −26.525 1.00 18.75 ATOM 3159CG PRO A 413 −11.513 31.928 −26.451 1.00 19.42 ATOM 3160 CD PRO A 413−10.943 33.195 −25.891 1.00 19.40 ATOM 3161 C PRO A 413 −7.959 31.399−25.464 1.00 18.87 ATOM 3162 O PRO A 413 −7.436 32.406 −25.955 1.0018.20 ATOM 3163 N LEU A 414 −7.253 30.353 −25.051 1.00 18.44 ATOM 3164CA LEU A 414 −5.822 30.275 −25.305 1.00 18.90 ATOM 3165 CB LEU A 414−4.992 30.974 −24.208 1.00 21.66 ATOM 3166 CG LEU A 414 −5.019 30.574−22.754 1.00 24.35 ATOM 3167 CD1 LEU A 414 −4.134 31.484 −21.892 1.0027.42 ATOM 3168 CD2 LEU A 414 −6.406 30.669 −22.224 1.00 30.77 ATOM 3169C LEU A 414 −5.362 28.854 −25.518 1.00 17.24 ATOM 3170 O LEU A 414−6.138 27.913 −25.406 1.00 15.97 ATOM 3171 N SER A 415 −4.091 28.733−25.865 1.00 15.34 ATOM 3172 CA SER A 415 −3.473 27.481 −26.257 1.0015.28 ATOM 3173 CB SER A 415 −3.434 26.468 −25.101 1.00 14.94 ATOM 3174OG SER A 415 −2.632 25.355 −25.445 1.00 14.00 ATOM 3175 C SER A 415−4.141 26.932 −27.528 1.00 15.13 ATOM 3176 O SER A 415 −4.665 27.718−28.334 1.00 14.92 ATOM 3177 N ALA A 416 −4.097 25.618 −27.714 1.0014.27 ATOM 3178 CA ALA A 416 −4.540 24.977 −28.976 1.00 14.25 ATOM 3179CB ALA A 416 −4.380 23.486 −28.889 1.00 13.68 ATOM 3180 C ALA A 416−5.981 25.314 −29.315 1.00 14.33 ATOM 3181 O ALA A 416 −6.854 25.216−28.459 1.00 14.09 ATOM 3182 N LEU A 417 −6.223 25.680 −30.567 1.0013.34 ATOM 3183 CA LEU A 417 −7.584 25.985 −31.006 1.00 14.22 ATOM 3184CB LEU A 417 −7.536 26.931 −32.194 1.00 16.32 ATOM 3185 CG LEU A 417−6.841 28.283 −31.942 1.00 18.75 ATOM 3186 CD1 LEU A 417 −7.005 29.127−33.163 1.00 23.81 ATOM 3187 CD2 LEU A 417 −7.419 28.991 −30.712 1.0021.76 ATOM 3188 C LEU A 417 −8.279 24.687 −31.413 1.00 13.18 ATOM 3189 OLEU A 417 −7.610 23.712 −31.775 1.00 13.19 ATOM 3190 N HIS A 418 −9.60924.658 −31.311 1.00 12.26 ATOM 3191 CA HIS A 418 −10.399 23.496 −31.7641.00 11.77 ATOM 3192 CB HIS A 418 −10.487 23.454 −33.303 1.00 13.41 ATOM3193 CG HIS A 418 −11.294 24.566 −33.898 1.00 14.68 ATOM 3194 ND1 HIS A418 −12.646 24.717 −33.660 1.00 16.00 ATOM 3195 CE1 HIS A 418 −13.09525.762 −34.341 1.00 17.83 ATOM 3196 NE2 HIS A 418 −12.085 26.290 −35.0151.00 17.38 ATOM 3197 CD2 HIS A 418 −10.948 25.557 −34.763 1.00 17.65ATOM 3198 C HIS A 418 −9.826 22.187 −31.206 1.00 12.24 ATOM 3199 O HIS A418 −9.540 21.250 −31.947 1.00 12.10 ATOM 3200 N LEU A 419 −9.656 22.116−29.880 1.00 10.99 ATOM 3201 CA LEU A 419 −9.152 20.881 −29.301 1.0010.46 ATOM 3202 CB LEU A 419 −8.742 21.069 −27.826 1.00 10.91 ATOM 3203CG LEU A 419 −7.983 19.883 −27.220 1.00 10.16 ATOM 3204 CD1 LEU A 419−6.524 19.944 −27.669 1.00 11.45 ATOM 3205 CD2 LEU A 419 −8.080 19.960−25.657 1.00 10.73 ATOM 3206 C LEU A 419 −10.215 19.812 −29.398 1.0010.49 ATOM 3207 O LEU A 419 −11.312 19.973 −28.863 1.00 10.67 ATOM 3208N THR A 420 −9.860 18.686 −30.021 1.00 10.22 ATOM 3209 CA THR A 420−10.833 17.629 −30.296 1.00 10.90 ATOM 3210 CB THR A 420 −10.201 16.460−31.096 1.00 11.55 ATOM 3211 OG1 THR A 420 −9.357 16.999 −32.115 1.0012.00 ATOM 3212 CG2 THR A 420 −11.310 15.625 −31.786 1.00 12.52 ATOM3213 C THR A 420 −11.426 17.135 −28.995 1.00 11.43 ATOM 3214 O THR A 420−12.648 16.903 −28.891 1.00 11.83 ATOM 3215 N TRP A 421 −10.569 16.987−27.980 1.00 9.79 ATOM 3216 CA TRP A 421 −11.052 16.511 −26.688 1.0011.67 ATOM 3217 CB TRP A 421 −9.839 16.184 −25.803 1.00 12.06 ATOM 3218CG TRP A 421 −10.075 15.476 −24.508 1.00 11.94 ATOM 3219 CD1 TRP A 421−11.274 15.202 −23.881 1.00 14.46 ATOM 3220 NE1 TRP A 421 −11.044 14.590−22.663 1.00 14.38 ATOM 3221 CE2 TRP A 421 −9.691 14.497 −22.468 1.0013.52 ATOM 3222 CD2 TRP A 421 −9.053 15.039 −23.616 1.00 13.01 ATOM 3223CE3 TRP A 421 −7.652 15.045 −23.680 1.00 15.38 ATOM 3224 CZ3 TRP A 421−6.932 14.503 −22.605 1.00 16.10 ATOM 3225 CH2 TRP A 421 −7.603 13.973−21.475 1.00 14.87 ATOM 3226 CZ2 TRP A 421 −8.973 13.945 −21.398 1.0014.27 ATOM 3227 C TRP A 421 −12.035 17.514 −26.032 1.00 10.89 ATOM 3228O TRP A 421 −12.966 17.092 −25.357 1.00 10.96 ATOM 3229 N SER A 422−11.844 18.822 −26.211 1.00 10.49 ATOM 3230 CA SER A 422 −12.833 19.794−25.696 1.00 11.13 ATOM 3231 CB SER A 422 −12.459 21.243 −26.049 1.0010.97 ATOM 3232 OG SER A 422 −11.302 21.682 −25.338 1.00 13.73 ATOM 3233C SER A 422 −14.229 19.496 −26.257 1.00 11.40 ATOM 3234 O SER A 422−15.204 19.468 −25.530 1.00 12.11 ATOM 3235 N TYR A 423 −14.320 19.281−27.563 1.00 11.29 ATOM 3236 CA TYR A 423 −15.617 18.990 −28.170 1.0011.29 ATOM 3237 CB TYR A 423 −15.502 19.020 −29.717 1.00 11.85 ATOM 3238CG TYR A 423 −15.132 20.389 −30.274 1.00 12.18 ATOM 3239 CD1 TYR A 423−16.002 21.485 −30.145 1.00 10.35 ATOM 3240 CE1 TYR A 423 −15.668 22.741−30.643 1.00 11.83 ATOM 3241 CZ TYR A 423 −14.468 22.912 −31.316 1.0012.29 ATOM 3242 OH TYR A 423 −14.157 24.145 −31.783 1.00 13.08 ATOM 3243CE2 TYR A 423 −13.588 21.845 −31.496 1.00 13.57 ATOM 3244 CD2 TYR A 423−13.942 20.572 −30.991 1.00 12.74 ATOM 3245 C TYR A 423 −16.217 17.673−27.658 1.00 12.12 ATOM 3246 O TYR A 423 −17.430 17.622 −27.323 1.0012.13 ATOM 3247 N ALA A 424 −15.385 16.623 −27.539 1.00 10.99 ATOM 3248CA ALA A 424 −15.853 15.337 −26.986 1.00 11.26 ATOM 3249 CB ALA A 424−14.717 14.294 −26.952 1.00 11.73 ATOM 3250 C ALA A 424 −16.411 15.535−25.588 1.00 10.93 ATOM 3251 O ALA A 424 −17.465 14.974 −25.246 1.0011.68 ATOM 3252 N SER A 425 −15.696 16.308 −24.770 1.00 9.74 ATOM 3253CA SER A 425 −16.077 16.519 −23.379 1.00 10.92 ATOM 3254 CB SER A 425−14.948 17.228 −22.602 1.00 11.59 ATOM 3255 OG SER A 425 −14.817 18.604−22.957 1.00 13.86 ATOM 3256 C SER A 425 −17.402 17.291 −23.219 1.0011.65 ATOM 3257 O SER A 425 −18.132 17.043 −22.276 1.00 11.86 ATOM 3258N PHE A 426 −17.683 18.220 −24.133 1.00 12.13 ATOM 3259 CA PHE A 426−18.983 18.891 −24.154 1.00 12.95 ATOM 3260 CB PHE A 426 −19.018 20.053−25.173 1.00 13.14 ATOM 3261 CG PHE A 426 −20.410 20.575 −25.391 1.0015.93 ATOM 3262 CD1 PHE A 426 −20.951 21.522 −24.516 1.00 17.76 ATOM3263 CE1 PHE A 426 −22.279 21.980 −24.688 1.00 17.49 ATOM 3264 CZ PHE A426 −23.064 21.455 −25.716 1.00 17.22 ATOM 3265 CE2 PHE A 426 −22.56120.496 −26.558 1.00 17.04 ATOM 3266 CD2 PHE A 426 −21.225 20.045 −26.3961.00 17.29 ATOM 3267 C PHE A 426 −20.079 17.878 −24.502 1.00 13.31 ATOM3268 O PHE A 426 −21.120 17.827 −23.850 1.00 13.38 ATOM 3269 N LEU A 427−19.834 17.077 −25.539 1.00 13.23 ATOM 3270 CA LEU A 427 −20.811 16.090−25.996 1.00 14.41 ATOM 3271 CB LEU A 427 −20.339 15.410 −27.291 1.0014.32 ATOM 3272 CG LEU A 427 −20.363 16.336 −28.506 1.00 15.96 ATOM 3273CD1 LEU A 427 −19.661 15.639 −29.689 1.00 18.66 ATOM 3274 CD2 LEU A 427−21.773 16.800 −28.876 1.00 16.20 ATOM 3275 C LEU A 427 −21.137 15.045−24.959 1.00 14.86 ATOM 3276 O LEU A 427 −22.307 14.667 −24.833 1.0016.01 ATOM 3277 N THR A 428 −20.130 14.551 −24.235 1.00 13.81 ATOM 3278CA THR A 428 −20.397 13.544 −23.196 1.00 13.67 ATOM 3279 CB THR A 428−19.134 12.732 −22.745 1.00 12.87 ATOM 3280 OG1 THR A 428 −18.127 13.597−22.185 1.00 12.33 ATOM 3281 CG2 THR A 428 −18.533 11.902 −23.923 1.0013.77 ATOM 3282 C THR A 428 −21.146 14.133 −21.980 1.00 13.66 ATOM 3283O THR A 428 −22.102 13.517 −21.478 1.00 15.09 ATOM 3284 N ALA A 429−20.738 15.312 −21.524 1.00 13.72 ATOM 3285 CA ALA A 429 −21.367 15.942−20.355 1.00 14.65 ATOM 3286 CB ALA A 429 −20.704 17.295 −20.036 1.0014.11 ATOM 3287 C ALA A 429 −22.852 16.158 −20.643 1.00 15.47 ATOM 3288O ALA A 429 −23.704 15.908 −19.783 1.00 15.97 ATOM 3289 N THR A 430−23.151 16.622 −21.854 1.00 15.48 ATOM 3290 CA THR A 430 −24.554 16.940−22.208 1.00 15.64 ATOM 3291 CB THR A 430 −24.675 17.968 −23.353 1.0016.50 ATOM 3292 OG1 THR A 430 −23.980 17.494 −24.514 1.00 16.24 ATOM3293 CG2 THR A 430 −24.101 19.317 −22.916 1.00 16.43 ATOM 3294 C THR A430 −25.401 15.690 −22.463 1.00 15.41 ATOM 3295 O THR A 430 −26.61115.674 −22.158 1.00 15.67 ATOM 3296 N ALA A 431 −24.772 14.632 −22.9681.00 15.22 ATOM 3297 CA ALA A 431 −25.437 13.311 −23.049 1.00 16.26 ATOM3298 CB ALA A 431 −24.560 12.300 −23.762 1.00 16.39 ATOM 3299 C ALA A431 −25.842 12.797 −21.673 1.00 16.53 ATOM 3300 O ALA A 431 −26.98512.319 −21.485 1.00 16.61 ATOM 3301 N ARG A 432 −24.937 12.895 −20.6891.00 15.66 ATOM 3302 CA ARG A 432 −25.256 12.410 −19.342 1.00 15.64 ATOM3303 CB ARG A 432 −24.022 12.413 −18.432 1.00 15.83 ATOM 3304 CG ARG A432 −22.862 11.574 −18.994 1.00 14.85 ATOM 3305 CD ARG A 432 −23.17410.051 −19.154 1.00 17.10 ATOM 3306 NE ARG A 432 −21.958 9.472 −19.7081.00 18.67 ATOM 3307 CZ ARG A 432 −21.766 9.225 −21.003 1.00 20.81 ATOM3308 NH1 ARG A 432 −22.769 9.372 −21.868 1.00 17.45 ATOM 3309 NH2 ARG A432 −20.576 8.781 −21.427 1.00 19.90 ATOM 3310 C ARG A 432 −26.37513.235 −18.719 1.00 16.42 ATOM 3311 O ARG A 432 −27.256 12.685 −18.0301.00 17.47 ATOM 3312 N ARG A 433 −26.371 14.535 −18.996 1.00 16.54 ATOM3313 CA ARG A 433 −27.425 15.418 −18.493 1.00 17.60 ATOM 3314 CB ARG A433 −27.204 16.852 −18.960 1.00 16.74 ATOM 3315 CG ARG A 433 −28.28717.833 −18.461 1.00 18.39 ATOM 3316 CD ARG A 433 −27.931 19.239 −18.8661.00 20.79 ATOM 3317 NE ARG A 433 −28.739 20.260 −18.166 1.00 23.05 ATOM3318 CZ ARG A 433 −29.859 20.799 −18.654 1.00 26.97 ATOM 3319 NH1 ARG A433 −30.333 20.404 −19.837 1.00 24.94 ATOM 3320 NH2 ARG A 433 −30.50621.738 −17.954 1.00 25.73 ATOM 3321 C ARG A 433 −28.793 14.943 −18.9561.00 17.90 ATOM 3322 O ARG A 433 −29.761 14.984 −18.184 1.00 18.50 ATOM3323 N ALA A 434 −28.861 14.502 −20.210 1.00 18.06 ATOM 3324 CA ALA A434 −30.103 13.993 −20.806 1.00 19.10 ATOM 3325 CB ALA A 434 −30.06714.202 −22.318 1.00 19.95 ATOM 3326 C ALA A 434 −30.399 12.532 −20.4751.00 20.48 ATOM 3327 O ALA A 434 −31.371 11.975 −20.980 1.00 21.63 ATOM3328 N GLY A 435 −29.594 11.904 −19.620 1.00 19.94 ATOM 3329 CA GLY A435 −29.865 10.531 −19.182 1.00 21.09 ATOM 3330 C GLY A 435 −29.4159.475 −20.188 1.00 21.57 ATOM 3331 O GLY A 435 −29.847 8.304 −20.1301.00 21.64 ATOM 3332 N ILE A 436 −28.529 9.873 −21.100 1.00 20.44 ATOM3333 CA ILE A 436 −27.951 8.937 −22.060 1.00 20.81 ATOM 3334 CB ILE A436 −27.753 9.601 −23.447 1.00 20.75 ATOM 3335 CG1 ILE A 436 −29.1329.977 −24.027 1.00 23.03 ATOM 3336 CD1 ILE A 436 −29.103 11.031 −25.1281.00 26.34 ATOM 3337 CG2 ILE A 436 −27.031 8.643 −24.395 1.00 21.35 ATOM3338 C ILE A 436 −26.634 8.412 −21.485 1.00 20.99 ATOM 3339 O ILE A 436−25.666 9.171 −21.339 1.00 20.46 ATOM 3340 N VAL A 437 −26.616 7.120−21.162 1.00 20.70 ATOM 3341 CA VAL A 437 −25.465 6.479 −20.517 1.0021.39 ATOM 3342 CB VAL A 437 −25.848 5.826 −19.160 1.00 21.74 ATOM 3343CG1 VAL A 437 −26.340 6.911 −18.205 1.00 22.12 ATOM 3344 CG2 VAL A 437−26.909 4.703 −19.334 1.00 21.83 ATOM 3345 C VAL A 437 −24.802 5.459−21.444 1.00 21.79 ATOM 3346 O VAL A 437 −25.459 4.901 −22.312 1.0022.18 ATOM 3347 N PRO A 438 −23.497 5.208 −21.255 1.00 22.28 ATOM 3348CA PRO A 438 −22.837 4.291 −22.181 1.00 22.83 ATOM 3349 CB PRO A 438−21.365 4.642 −22.009 1.00 22.45 ATOM 3350 CG PRO A 438 −21.248 5.054−20.578 1.00 23.88 ATOM 3351 CD PRO A 438 −22.575 5.707 −20.214 1.0022.50 ATOM 3352 C PRO A 438 −23.093 2.840 −21.753 1.00 22.80 ATOM 3353 OPRO A 438 −23.580 2.604 −20.626 1.00 23.06 ATOM 3354 N PRO A 439 −22.7961.878 −22.639 1.00 22.65 ATOM 3355 CA PRO A 439 −22.911 0.452 −22.2831.00 22.08 ATOM 3356 CB PRO A 439 −22.300 −0.269 −23.499 1.00 21.30 ATOM3357 CG PRO A 439 −22.526 0.664 −24.618 1.00 22.81 ATOM 3358 CD PRO A439 −22.391 2.062 −24.050 1.00 22.29 ATOM 3359 C PRO A 439 −22.122 0.129−21.037 1.00 21.88 ATOM 3360 O PRO A 439 −21.075 0.750 −20.776 1.0020.95 ATOM 3361 N SER A 440 −22.628 −0.818 −20.253 1.00 22.34 ATOM 3362CA SER A 440 −21.932 −1.273 −19.060 1.00 23.42 ATOM 3363 CB SER A 440−22.818 −2.195 −18.224 1.00 24.01 ATOM 3364 OG SER A 440 −23.805 −1.412−17.566 1.00 26.78 ATOM 3365 C SER A 440 −20.654 −1.992 −19.430 1.0023.78 ATOM 3366 O SER A 440 −20.540 −2.554 −20.522 1.00 23.97 ATOM 3367N TRP A 441 −19.681 −1.929 −18.536 1.00 24.15 ATOM 3368 CA TRP A 441−18.431 −2.646 −18.718 1.00 24.63 ATOM 3369 CB TRP A 441 −17.255 −1.679−18.819 1.00 22.62 ATOM 3370 CG TRP A 441 −16.963 −0.837 −17.583 1.0019.24 ATOM 3371 CD1 TRP A 441 −17.409 0.432 −17.339 1.00 16.95 ATOM 3372NE1 TRP A 441 −16.909 0.878 −16.138 1.00 17.89 ATOM 3373 CE2 TRP A 441−16.111 −0.098 −15.595 1.00 17.88 ATOM 3374 CD2 TRP A 441 −16.130 −1.194−16.476 1.00 18.22 ATOM 3375 CE3 TRP A 441 −15.377 −2.338 −16.149 1.0019.64 ATOM 3376 CZ3 TRP A 441 −14.658 −2.355 −14.961 1.00 18.61 ATOM3377 CH2 TRP A 441 −14.670 −1.246 −14.094 1.00 20.62 ATOM 3378 CZ2 TRP A441 −15.400 −0.114 −14.391 1.00 19.39 ATOM 3379 C TRP A 441 −18.179−3.661 −17.625 1.00 26.71 ATOM 3380 O TRP A 441 −17.410 −4.592 −17.8131.00 25.60 ATOM 3381 N ALA A 442 −18.798 −3.471 −16.468 1.00 29.78 ATOM3382 CA ALA A 442 −18.442 −4.292 −15.330 1.00 33.94 ATOM 3383 CB ALA A442 −18.347 −3.447 −14.082 1.00 33.18 ATOM 3384 C ALA A 442 −19.447−5.412 −15.136 1.00 37.28 ATOM 3385 O ALA A 442 −20.383 −5.561 −15.9151.00 38.51 ATOM 3386 N ASN A 443 −19.201 −6.222 −14.116 1.00 41.45 ATOM3387 CA ASN A 443 −20.226 −7.030 −13.467 1.00 45.10 ATOM 3388 CB ASN A443 −20.135 −8.490 −13.914 1.00 45.75 ATOM 3389 CG ASN A 443 −18.815−9.129 −13.531 1.00 48.14 ATOM 3390 OD1 ASN A 443 −18.620 −9.524 −12.3801.00 50.51 ATOM 3391 ND2 ASN A 443 −17.888 −9.212 −14.492 1.00 50.01ATOM 3392 C ASN A 443 −19.946 −6.892 −11.972 1.00 46.93 ATOM 3393 O ASNA 443 −18.878 −6.396 −11.580 1.00 47.13 ATOM 3394 N SER A 444 −20.873−7.343 −11.135 1.00 49.21 ATOM 3395 CA SER A 444 −20.719 −7.201 −9.6841.00 51.08 ATOM 3396 CB SER A 444 −21.713 −8.096 −8.936 1.00 51.21 ATOM3397 OG SER A 444 −21.738 −7.735 −7.563 1.00 52.90 ATOM 3398 C SER A 444−19.291 −7.452 −9.165 1.00 51.89 ATOM 3399 O SER A 444 −18.743 −6.610−8.433 1.00 52.46 ATOM 3400 N SER A 445 −18.700 −8.588 −9.558 1.00 52.45ATOM 3401 CA SER A 445 −17.400 −9.030 −9.029 1.00 52.98 ATOM 3402 CB SERA 445 −17.138 −10.497 −9.385 1.00 53.12 ATOM 3403 OG SER A 445 −16.901−10.650 −10.775 1.00 54.45 ATOM 3404 C SER A 445 −16.202 −8.159 −9.4491.00 52.99 ATOM 3405 O SER A 445 −15.184 −8.112 −8.738 1.00 53.28 ATOM3406 N ALA A 446 −16.328 −7.472 −10.588 1.00 52.67 ATOM 3407 CA ALA A446 −15.301 −6.536 −11.063 1.00 52.20 ATOM 3408 CB ALA A 446 −15.695−5.960 −12.425 1.00 52.45 ATOM 3409 C ALA A 446 −14.996 −5.406 −10.0591.00 51.92 ATOM 3410 O ALA A 446 −14.144 −4.553 −10.322 1.00 51.77 ATOM3411 N SER A 447 −15.696 −5.413 −8.919 1.00 51.23 ATOM 3412 CA SER A 447−15.471 −4.453 −7.827 1.00 50.73 ATOM 3413 CB SER A 447 −16.769 −3.706−7.495 1.00 50.70 ATOM 3414 OG SER A 447 −17.765 −4.605 −7.021 1.0050.91 ATOM 3415 C SER A 447 −14.886 −5.072 −6.537 1.00 50.31 ATOM 3416 OSER A 447 −14.604 −4.345 −5.580 1.00 50.16 ATOM 3417 N THR A 448 −14.704−6.394 −6.508 1.00 49.55 ATOM 3418 CA THR A 448 −14.165 −7.070 −5.3141.00 49.05 ATOM 3419 CB THR A 448 −14.579 −8.561 −5.233 1.00 49.15 ATOM3420 OG1 THR A 448 −14.076 −9.255 −6.378 1.00 49.97 ATOM 3421 CG2 THR A448 −16.096 −8.705 −5.180 1.00 49.11 ATOM 3422 C THR A 448 −12.641−6.958 −5.215 1.00 48.34 ATOM 3423 O THR A 448 −11.911 −7.325 −6.1351.00 47.84 ATOM 3424 N ILE A 449 −12.174 −6.444 −4.084 1.00 47.93 ATOM3425 CA ILE A 449 −10.760 −6.150 −3.891 1.00 47.42 ATOM 3426 CB ILE A449 −10.577 −4.798 −3.142 1.00 47.53 ATOM 3427 CG1 ILE A 449 −11.346−3.680 −3.863 1.00 46.60 ATOM 3428 CD1 ILE A 449 −11.727 −2.523 −2.9811.00 45.49 ATOM 3429 CG2 ILE A 449 −9.097 −4.438 −2.999 1.00 46.84 ATOM3430 C ILE A 449 −10.104 −7.299 −3.124 1.00 47.45 ATOM 3431 O ILE A 449−10.606 −7.688 −2.067 1.00 47.66 ATOM 3432 N PRO A 450 −8.993 −7.857−3.663 1.00 47.28 ATOM 3433 CA PRO A 450 −8.202 −8.926 −3.036 1.00 47.25ATOM 3434 CB PRO A 450 −6.982 −9.040 −3.946 1.00 47.03 ATOM 3435 CG PROA 450 −7.430 −8.535 −5.237 1.00 47.02 ATOM 3436 CD PRO A 450 −8.431−7.470 −4.969 1.00 47.07 ATOM 3437 C PRO A 450 −7.731 −8.562 −1.639 1.0047.48 ATOM 3438 O PRO A 450 −7.608 −7.377 −1.322 1.00 47.43 ATOM 3439 NSER A 451 −7.452 −9.587 −0.832 1.00 47.94 ATOM 3440 CA SER A 451 −7.020−9.436 0.568 1.00 48.19 ATOM 3441 CB SER A 451 −7.017 −10.801 1.277 1.0048.52 ATOM 3442 OG SER A 451 −8.297 −11.414 1.235 1.00 49.64 ATOM 3443 CSER A 451 −5.641 −8.799 0.701 1.00 47.83 ATOM 3444 O SER A 451 −5.415−7.963 1.575 1.00 48.39 ATOM 3445 N THR A 452 −4.715 −9.212 −0.158 1.0047.14 ATOM 3446 CA THR A 452 −3.379 −8.613 −0.211 1.00 46.42 ATOM 3447CB THR A 452 −2.323 −9.540 0.434 1.00 46.66 ATOM 3448 OG1 THR A 452−2.518 −10.887 −0.032 1.00 48.38 ATOM 3449 CG2 THR A 452 −2.446 −9.5141.962 1.00 47.77 ATOM 3450 C THR A 452 −3.011 −8.323 −1.673 1.00 44.81ATOM 3451 O THR A 452 −3.348 −9.107 −2.558 1.00 44.97 ATOM 3452 N CYS A453 −2.363 −7.187 −1.931 1.00 43.37 ATOM 3453 CA CYS A 453 −1.971 −6.854−3.306 1.00 41.40 ATOM 3454 CB CYS A 453 −1.918 −5.339 −3.574 1.00 41.01ATOM 3455 SG CYS A 453 −3.187 −4.199 −2.908 1.00 40.58 ATOM 3456 C CYS A453 −0.591 −7.408 −3.602 1.00 40.33 ATOM 3457 O CYS A 453 0.293 −7.370−2.753 1.00 39.88 ATOM 3458 N SER A 454 −0.405 −7.911 −4.812 1.00 39.25ATOM 3459 CA SER A 454 0.937 −8.142 −5.336 1.00 38.68 ATOM 3460 CB SER A454 1.222 −9.638 −5.484 1.00 38.56 ATOM 3461 OG SER A 454 0.276 −10.251−6.349 1.00 40.44 ATOM 3462 C SER A 454 1.047 −7.450 −6.690 1.00 37.78ATOM 3463 O SER A 454 0.030 −7.187 −7.347 1.00 36.71 ATOM 3464 N GLY A455 2.275 −7.175 −7.111 1.00 37.06 ATOM 3465 CA GLY A 455 2.514 −6.613−8.431 1.00 36.79 ATOM 3466 C GLY A 455 2.493 −7.658 −9.539 1.00 36.18ATOM 3467 O GLY A 455 3.410 −7.708 −10.367 1.00 36.73 ATOM 3468 N ALA A456 1.445 −8.480 −9.562 1.00 35.26 ATOM 3469 CA ALA A 456 1.321 −9.584−10.512 1.00 34.46 ATOM 3470 CB ALA A 456 0.125 −10.454 −10.158 1.0034.50 ATOM 3471 C ALA A 456 1.195 −9.111 −11.963 1.00 34.16 ATOM 3472 OALA A 456 0.283 −8.353 −12.301 1.00 33.56 ATOM 3473 N SER A 457 2.097−9.588 −12.817 1.00 33.11 ATOM 3474 CA SER A 457 2.013 −9.302 −14.2411.00 32.60 ATOM 3475 CB SER A 457 3.022 −8.219 −14.635 1.00 32.50 ATOM3476 OG SER A 457 4.352 −8.691 −14.519 1.00 33.28 ATOM 3477 C SER A 4572.228 −10.575 −15.044 1.00 32.31 ATOM 3478 O SER A 457 2.641 −11.605−14.494 1.00 32.32 ATOM 3479 N VAL A 458 1.908 −10.511 −16.330 1.0031.12 ATOM 3480 CA VAL A 458 2.063 −11.629 −17.246 1.00 31.09 ATOM 3481CB VAL A 458 0.682 −12.199 −17.659 1.00 31.00 ATOM 3482 CG1 VAL A 4580.806 −13.173 −18.830 1.00 30.72 ATOM 3483 CG2 VAL A 458 −0.014 −12.847−16.459 1.00 31.08 ATOM 3484 C VAL A 458 2.817 −11.144 −18.480 1.0030.88 ATOM 3485 O VAL A 458 2.401 −10.177 −19.126 1.00 29.70 ATOM 3486 NVAL A 459 3.924 −11.811 −18.805 1.00 30.81 ATOM 3487 CA VAL A 459 4.643−11.525 −20.051 1.00 30.95 ATOM 3488 CB VAL A 459 6.046 −12.172 −20.0711.00 31.34 ATOM 3489 CG1 VAL A 459 6.664 −12.102 −21.492 1.00 30.45 ATOM3490 CG2 VAL A 459 6.947 −11.522 −19.030 1.00 32.03 ATOM 3491 C VAL A459 3.805 −12.032 −21.227 1.00 31.37 ATOM 3492 O VAL A 459 3.443 −13.214−21.288 1.00 31.84 ATOM 3493 N GLY A 460 3.480 −11.137 −22.154 1.0030.71 ATOM 3494 CA GLY A 460 2.596 −11.495 −23.258 1.00 30.77 ATOM 3495C GLY A 460 3.349 −11.799 −24.536 1.00 30.66 ATOM 3496 O GLY A 460 4.585−11.773 −24.582 1.00 30.90 ATOM 3497 N SER A 461 2.606 −12.094 −25.5841.00 30.44 ATOM 3498 CA SER A 461 3.219 −12.227 −26.877 1.00 31.06 ATOM3499 CB SER A 461 3.301 −13.695 −27.308 1.00 31.44 ATOM 3500 OG SER A461 2.018 −14.278 −27.419 1.00 34.77 ATOM 3501 C SER A 461 2.463 −11.357−27.864 1.00 30.21 ATOM 3502 O SER A 461 1.246 −11.156 −27.736 1.0030.87 ATOM 3503 N TYR A 462 3.192 −10.822 −28.836 1.00 28.84 ATOM 3504CA TYR A 462 2.651 −9.797 −29.712 1.00 28.13 ATOM 3505 CB TYR A 4623.365 −8.471 −29.426 1.00 26.74 ATOM 3506 CG TYR A 462 3.264 −8.096−27.976 1.00 25.28 ATOM 3507 CD1 TYR A 462 2.184 −7.335 −27.508 1.0023.75 ATOM 3508 CE1 TYR A 462 2.066 −7.022 −26.162 1.00 23.41 ATOM 3509CZ TYR A 462 3.030 −7.458 −25.268 1.00 23.32 ATOM 3510 OH TYR A 4622.907 −7.155 −23.941 1.00 23.50 ATOM 3511 CE2 TYR A 462 4.113 −8.226−25.698 1.00 22.57 ATOM 3512 CD2 TYR A 462 4.223 −8.537 −27.050 1.0024.71 ATOM 3513 C TYR A 462 2.844 −10.191 −31.152 1.00 28.83 ATOM 3514 OTYR A 462 3.898 −10.697 −31.529 1.00 29.33 ATOM 3515 N SER A 463 1.828−9.973 −31.961 1.00 29.66 ATOM 3516 CA SER A 463 1.970 −10.202 −33.3881.00 30.77 ATOM 3517 CB SER A 463 1.424 −11.574 −33.784 1.00 30.99 ATOM3518 OG SER A 463 0.168 −11.815 −33.192 1.00 33.22 ATOM 3519 C SER A 4631.311 −9.082 −34.170 1.00 31.28 ATOM 3520 O SER A 463 0.329 −8.481−33.723 1.00 30.40 ATOM 3521 N ARG A 464 1.886 −8.789 −35.330 1.00 31.94ATOM 3522 CA ARG A 464 1.377 −7.775 −36.225 1.00 32.97 ATOM 3523 CB ARGA 464 2.362 −7.620 −37.385 1.00 33.68 ATOM 3524 CG ARG A 464 2.353−6.274 −38.061 1.00 36.94 ATOM 3525 CD ARG A 464 3.502 −6.206 −39.0881.00 42.45 ATOM 3526 NE ARG A 464 4.794 −6.065 −38.415 1.00 45.53 ATOM3527 CZ ARG A 464 5.416 −4.903 −38.227 1.00 47.50 ATOM 3528 NH1 ARG A464 4.882 −3.775 −38.688 1.00 49.50 ATOM 3529 NH2 ARG A 464 6.580 −4.863−37.592 1.00 48.59 ATOM 3530 C ARG A 464 −0.017 −8.171 −36.741 1.0033.03 ATOM 3531 O ARG A 464 −0.166 −9.228 −37.358 1.00 33.00 ATOM 3532 NPRO A 465 −1.053 −7.333 −36.479 1.00 32.72 ATOM 3533 CA PRO A 465 −2.344−7.593 −37.131 1.00 32.69 ATOM 3534 CB PRO A 465 −3.274 −6.504 −36.5581.00 32.50 ATOM 3535 CG PRO A 465 −2.581 −5.981 −35.345 1.00 32.47 ATOM3536 CD PRO A 465 −1.102 −6.134 −35.618 1.00 32.83 ATOM 3537 C PRO A 465−2.189 −7.421 −38.642 1.00 33.30 ATOM 3538 O PRO A 465 −1.332 −6.661−39.097 1.00 33.20 ATOM 3539 N THR A 466 −2.990 −8.136 −39.412 1.0034.26 ATOM 3540 CA THR A 466 −2.810 −8.131 −40.855 1.00 35.62 ATOM 3541CB THR A 466 −2.264 −9.486 −41.370 1.00 35.33 ATOM 3542 OG1 THR A 466−3.225 −10.512 −41.136 1.00 36.81 ATOM 3543 CG2 THR A 466 −0.965 −9.848−40.656 1.00 35.91 ATOM 3544 C THR A 466 −4.076 −7.711 −41.600 1.0036.15 ATOM 3545 O THR A 466 −3.983 −7.077 −42.648 1.00 36.93 ATOM 3546 NALA A 467 −5.242 −8.051 −41.048 1.00 36.82 ATOM 3547 CA ALA A 467 −6.540−7.648 −41.509 1.00 37.30 ATOM 3548 CB ALA A 467 −7.663 −8.403 −40.9301.00 37.04 ATOM 3549 C ALA A 467 −6.767 −6.136 −41.509 1.00 38.13 ATOM3550 O ALA A 467 −6.715 −5.556 −40.417 1.00 37.96 ATOM 3551 N THR A 468−7.011 −5.502 −42.653 1.00 38.66 ATOM 3552 CA THR A 468 −7.146 −4.050−42.702 1.00 39.18 ATOM 3553 CB THR A 468 −5.970 −3.406 −43.428 1.0039.43 ATOM 3554 OG1 THR A 468 −5.955 −3.879 −44.778 1.00 40.06 ATOM 3555CG2 THR A 468 −4.637 −3.717 −42.734 1.00 39.67 ATOM 3556 C THR A 468−8.405 −3.591 −43.427 1.00 39.33 ATOM 3557 O THR A 468 −8.468 −2.451−43.890 1.00 39.79 ATOM 3558 N SER A 469 −9.403 −4.457 −43.529 1.0039.12 ATOM 3559 CA SER A 469 −10.651 −4.065 −44.176 1.00 39.41 ATOM 3560CB SER A 469 −10.624 −4.369 −45.684 1.00 39.77 ATOM 3561 OG SER A 469−10.476 −5.763 −45.916 1.00 41.02 ATOM 3562 C SER A 469 −11.850 −4.732−43.537 1.00 38.54 ATOM 3563 O SER A 469 −11.771 −5.856 −43.046 1.0038.85 ATOM 3564 N PHE A 470 −12.962 −4.014 −43.558 1.00 38.00 ATOM 3565CA PHE A 470 −14.216 −4.507 −43.031 1.00 37.29 ATOM 3566 CB PHE A 470−14.880 −3.406 −42.220 1.00 36.87 ATOM 3567 CG PHE A 470 −14.277 −3.212−40.865 1.00 35.43 ATOM 3568 CD1 PHE A 470 −13.146 −2.428 −40.696 1.0035.15 ATOM 3569 CE1 PHE A 470 −12.589 −2.252 −39.437 1.00 33.73 ATOM3570 CZ PHE A 470 −13.159 −2.852 −38.332 1.00 35.04 ATOM 3571 CE2 PHE A470 −14.292 −3.638 −38.479 1.00 36.26 ATOM 3572 CD2 PHE A 470 −14.844−3.816 −39.751 1.00 35.71 ATOM 3573 C PHE A 470 −15.128 −4.923 −44.1811.00 37.34 ATOM 3574 O PHE A 470 −15.059 −4.337 −45.258 1.00 37.21 ATOM3575 N PRO A 471 −15.987 −5.931 −43.959 1.00 37.46 ATOM 3576 CA PRO A471 −16.983 −6.243 −44.985 1.00 38.04 ATOM 3577 CB PRO A 471 −17.790−7.383 −44.361 1.00 37.60 ATOM 3578 CG PRO A 471 −16.877 −7.986 −43.3371.00 38.09 ATOM 3579 CD PRO A 471 −16.093 −6.828 −42.795 1.00 37.31 ATOM3580 C PRO A 471 −17.879 −5.033 −45.231 1.00 38.96 ATOM 3581 O PRO A 471−18.108 −4.245 −44.306 1.00 38.78 ATOM 3582 N PRO A 472 −18.378 −4.869−46.471 1.00 39.78 ATOM 3583 CA PRO A 472 −19.238 −3.723 −46.771 1.0039.87 ATOM 3584 CB PRO A 472 −19.378 −3.780 −48.293 1.00 40.09 ATOM 3585CG PRO A 472 −19.171 −5.225 −48.635 1.00 40.28 ATOM 3586 CD PRO A 472−18.171 −5.740 −47.649 1.00 40.02 ATOM 3587 C PRO A 472 −20.604 −3.864−46.114 1.00 39.75 ATOM 3588 O PRO A 472 −21.017 −4.980 −45.798 1.0040.10 ATOM 3589 N SER A 473 −21.268 −2.734 −45.881 1.00 39.71 ATOM 3590CA SER A 473 −22.675 −2.696 −45.467 1.00 39.61 ATOM 3591 CB SER A 473−23.571 −3.070 −46.651 1.00 40.16 ATOM 3592 OG SER A 473 −23.468 −2.074−47.658 1.00 42.55 ATOM 3593 C SER A 473 −23.043 −3.509 −44.221 1.0038.94 ATOM 3594 O SER A 473 −24.041 −4.258 −44.210 1.00 39.07 ATOM 3595N GLN A 474 −22.257 −3.340 −43.159 1.00 37.75 ATOM 3596 CA GLN A 474−22.558 −3.993 −41.888 1.00 36.60 ATOM 3597 CB GLN A 474 −21.291 −4.205−41.057 1.00 36.41 ATOM 3598 CG GLN A 474 −20.331 −5.169 −41.732 1.0036.24 ATOM 3599 CD GLN A 474 −19.295 −5.757 −40.795 1.00 36.45 ATOM 3600OE1 GLN A 474 −18.478 −5.040 −40.211 1.00 35.30 ATOM 3601 NE2 GLN A 474−19.304 −7.077 −40.671 1.00 36.85 ATOM 3602 C GLN A 474 −23.620 −3.191−41.149 1.00 36.40 ATOM 3603 O GLN A 474 −23.329 −2.444 −40.208 1.0035.99 ATOM 3604 N THR A 475 −24.859 −3.350 −41.616 1.00 35.59 ATOM 3605CA THR A 475 −26.012 −2.595 −41.148 1.00 35.20 ATOM 3606 CB THR A 475−27.051 −2.478 −42.287 1.00 35.73 ATOM 3607 OG1 THR A 475 −27.120 −3.737−42.959 1.00 36.85 ATOM 3608 CG2 THR A 475 −26.642 −1.418 −43.310 1.0034.51 ATOM 3609 C THR A 475 −26.635 −3.256 −39.910 1.00 35.16 ATOM 3610O THR A 475 −26.363 −4.420 −39.622 1.00 34.47 ATOM 3611 N PRO A 476−27.453 −2.510 −39.148 1.00 35.36 ATOM 3612 CA PRO A 476 −27.990 −3.111−37.923 1.00 36.40 ATOM 3613 CB PRO A 476 −28.567 −1.910 −37.167 1.0036.04 ATOM 3614 CG PRO A 476 −28.890 −0.912 −38.230 1.00 35.98 ATOM 3615CD PRO A 476 −27.907 −1.119 −39.339 1.00 35.70 ATOM 3616 C PRO A 476−29.085 −4.171 −38.158 1.00 37.45 ATOM 3617 O PRO A 476 −29.654 −4.244−39.254 1.00 36.95 ATOM 3618 N LYS A 477 −29.342 −4.984 −37.133 1.0039.01 ATOM 3619 CA LYS A 477 −30.472 −5.911 −37.111 1.00 41.20 ATOM 3620CB LYS A 477 −30.541 −6.641 −35.774 1.00 41.46 ATOM 3621 CG LYS A 477−29.665 −7.850 −35.604 1.00 41.87 ATOM 3622 CD LYS A 477 −29.939 −8.517−34.237 1.00 42.36 ATOM 3623 CB LYS A 477 −29.996 −7.497 −33.076 1.0044.55 ATOM 3624 NZ LYS A 477 −29.705 −8.110 −31.718 1.00 44.56 ATOM 3625C LYS A 477 −31.766 −5.118 −37.230 1.00 42.27 ATOM 3626 O LYS A 477−31.818 −3.960 −36.798 1.00 42.18 ATOM 3627 N PRO A 478 −32.831 −5.743−37.780 1.00 43.46 ATOM 3628 CA PRO A 478 −34.150 −5.106 −37.669 1.0044.02 ATOM 3629 CB PRO A 478 −35.106 −6.144 −38.267 1.00 43.89 ATOM 3630CG PRO A 478 −34.255 −7.033 −39.105 1.00 44.08 ATOM 3631 CD PRO A 478−32.885 −7.034 −38.493 1.00 43.41 ATOM 3632 C PRO A 478 −34.480 −4.892−36.194 1.00 44.52 ATOM 3633 O PRO A 478 −34.197 −5.769 −35.364 1.0044.73 ATOM 3634 N GLY A 479 −35.043 −3.728 −35.874 1.00 45.20 ATOM 3635CA GLY A 479 −35.421 −3.395 −34.494 1.00 45.90 ATOM 3636 C GLY A 479−34.386 −2.601 −33.711 1.00 46.37 ATOM 3637 O GLY A 479 −34.576 −2.331−32.520 1.00 46.98 ATOM 3638 N VAL A 480 −33.282 −2.244 −34.367 1.0046.28 ATOM 3639 CA VAL A 480 −32.261 −1.383 −33.760 1.00 46.15 ATOM 3640CB VAL A 480 −30.820 −1.863 −34.121 1.00 46.20 ATOM 3641 CG1 VAL A 480−29.755 −0.899 −33.584 1.00 45.85 ATOM 3642 CG2 VAL A 480 −30.569 −3.281−33.603 1.00 46.25 ATOM 3643 C VAL A 480 −32.498 0.046 −34.260 1.0045.93 ATOM 3644 O VAL A 480 −32.673 0.240 −35.465 1.00 46.15 ATOM 3645 NPRO A 481 −32.534 1.049 −33.344 1.00 45.70 ATOM 3646 CA PRO A 481−32.648 2.443 −33.804 1.00 45.36 ATOM 3647 CB PRO A 481 −32.388 3.266−32.542 1.00 45.39 ATOM 3648 CG PRO A 481 −32.778 2.375 −31.427 1.0045.52 ATOM 3649 CD PRO A 481 −32.481 0.962 −31.873 1.00 45.83 ATOM 3650C PRO A 481 −31.609 2.762 −34.877 1.00 45.08 ATOM 3651 O PRO A 481−30.405 2.555 −34.681 1.00 44.45 ATOM 3652 N SER A 482 −32.100 3.241−36.011 1.00 44.83 ATOM 3653 CA SER A 482 −31.281 3.485 −37.180 1.0044.52 ATOM 3654 CB SER A 482 −31.502 2.375 −38.211 1.00 44.74 ATOM 3655OG SER A 482 −30.769 2.622 −39.399 1.00 45.89 ATOM 3656 C SER A 482−31.661 4.836 −37.765 1.00 43.84 ATOM 3657 O SER A 482 −32.836 5.219−37.741 1.00 44.07 ATOM 3658 N GLY A 483 −30.667 5.550 −38.282 1.0042.68 ATOM 3659 CA GLY A 483 −30.872 6.872 −38.853 1.00 41.64 ATOM 3660C GLY A 483 −30.085 7.095 −40.130 1.00 41.05 ATOM 3661 O GLY A 483−29.430 6.179 −40.647 1.00 41.09 ATOM 3662 N THR A 484 −30.155 8.317−40.647 1.00 40.22 ATOM 3663 CA THR A 484 −29.461 8.677 −41.888 1.0039.91 ATOM 3664 CB THR A 484 −30.148 9.876 −42.619 1.00 40.21 ATOM 3665OG1 THR A 484 −30.115 11.040 −41.780 1.00 41.48 ATOM 3666 CG2 THR A 484−31.604 9.541 −43.000 1.00 40.86 ATOM 3667 C THR A 484 −27.995 9.033−41.603 1.00 38.43 ATOM 3668 O THR A 484 −27.669 9.421 −40.483 1.0038.52 ATOM 3669 N PRO A 485 −27.109 8.893 −42.612 1.00 37.36 ATOM 3670CA PRO A 485 −25.695 9.226 −42.413 1.00 36.29 ATOM 3671 CB PRO A 485−25.077 8.974 −43.795 1.00 36.75 ATOM 3672 CG PRO A 485 −25.997 7.985−44.442 1.00 37.04 ATOM 3673 CD PRO A 485 −27.359 8.393 −43.976 1.0037.30 ATOM 3674 C PRO A 485 −25.460 10.684 −41.988 1.00 35.20 ATOM 3675O PRO A 485 −26.201 11.599 −42.396 1.00 34.39 ATOM 3676 N TYR A 486−24.428 10.887 −41.174 1.00 33.60 ATOM 3677 CA TYR A 486 −24.025 12.233−40.782 1.00 32.74 ATOM 3678 CB TYR A 486 −22.821 12.180 −39.826 1.0032.31 ATOM 3679 CG TYR A 486 −22.348 13.564 −39.452 1.00 32.79 ATOM 3680CD1 TYR A 486 −21.243 14.146 −40.083 1.00 31.74 ATOM 3681 CE1 TYR A 486−20.827 15.430 −39.742 1.00 30.85 ATOM 3682 CZ TYR A 486 −21.527 16.141−38.778 1.00 31.99 ATOM 3683 OH TYR A 486 −21.143 17.423 −38.427 1.0032.20 ATOM 3684 CE2 TYR A 486 −22.629 15.588 −38.160 1.00 31.88 ATOM3685 CD2 TYR A 486 −23.036 14.311 −38.500 1.00 32.49 ATOM 3686 C TYR A486 −23.652 13.082 −41.999 1.00 31.99 ATOM 3687 O TYR A 486 −22.94912.602 −42.900 1.00 31.62 ATOM 3688 N THR A 487 −24.106 14.336 −42.0041.00 31.14 ATOM 3689 CA THR A 487 −23.676 15.336 −42.986 1.00 31.43 ATOM3690 CB THR A 487 −24.879 15.785 −43.869 1.00 31.94 ATOM 3691 OG1 THR A487 −25.321 14.665 −44.644 1.00 35.19 ATOM 3692 CG2 THR A 487 −24.48916.904 −44.810 1.00 32.95 ATOM 3693 C THR A 487 −23.110 16.561 −42.2611.00 29.79 ATOM 3694 O THR A 487 −23.761 17.078 −41.363 1.00 29.20 ATOM3695 N PRO A 488 −21.901 17.027 −42.644 1.00 29.20 ATOM 3696 CA PRO A488 −21.309 18.228 −42.005 1.00 28.77 ATOM 3697 CB PRO A 488 −19.98818.435 −42.763 1.00 28.75 ATOM 3698 CG PRO A 488 −19.684 17.126 −43.4081.00 29.52 ATOM 3699 CD PRO A 488 −21.010 16.448 −43.667 1.00 29.41 ATOM3700 C PRO A 488 −22.175 19.463 −42.194 1.00 28.44 ATOM 3701 O PRO A 488−23.003 19.499 −43.116 1.00 28.51 ATOM 3702 N LEU A 489 −21.971 20.469−41.345 1.00 27.28 ATOM 3703 CA LEU A 489 −22.606 21.775 −41.522 1.0026.52 ATOM 3704 CB LEU A 489 −22.269 22.708 −40.365 1.00 27.19 ATOM 3705CG LEU A 489 −22.805 22.303 −38.987 1.00 27.53 ATOM 3706 CD1 LEU A 489−22.233 23.242 −37.929 1.00 26.81 ATOM 3707 CD2 LEU A 489 −24.332 22.323−38.970 1.00 28.98 ATOM 3708 C LEU A 489 −22.137 22.402 −42.833 1.0026.65 ATOM 3709 O LEU A 489 −20.983 22.210 −43.245 1.00 25.40 ATOM 3710N PRO A 490 −23.030 23.153 −43.503 1.00 26.84 ATOM 3711 CA PRO A 490−22.636 23.745 −44.786 1.00 26.44 ATOM 3712 CB PRO A 490 −23.983 24.107−45.432 1.00 27.00 ATOM 3713 CG PRO A 490 −24.900 24.341 −44.289 1.0027.68 ATOM 3714 CD PRO A 490 −24.425 23.475 −43.137 1.00 26.91 ATOM 3715C PRO A 490 −21.737 24.982 −44.668 1.00 26.22 ATOM 3716 O PRO A 490−21.826 25.729 −43.698 1.00 25.74 ATOM 3717 N CYS A 491 −20.858 25.182−45.650 1.00 26.06 ATOM 3718 CA CYS A 491 −20.079 26.412 −45.754 1.0026.88 ATOM 3719 CB CYS A 491 −18.630 26.194 −45.302 1.00 27.00 ATOM 3720SG CYS A 491 −18.450 25.196 −43.819 1.00 27.23 ATOM 3721 C CYS A 491−20.032 26.822 −47.217 1.00 27.27 ATOM 3722 O CYS A 491 −20.369 26.026−48.083 1.00 27.34 ATOM 3723 N ALA A 492 −19.577 28.045 −47.484 1.0028.05 ATOM 3724 CA ALA A 492 −19.205 28.449 −48.845 1.00 29.40 ATOM 3725CB ALA A 492 −18.837 29.928 −48.866 1.00 29.49 ATOM 3726 C ALA A 492−18.023 27.599 −49.320 1.00 30.37 ATOM 3727 O ALA A 492 −17.310 26.998−48.497 1.00 30.36 ATOM 3728 N THR A 493 −17.828 27.508 −50.633 1.0031.27 ATOM 3729 CA THR A 493 −16.612 26.883 −51.163 1.00 32.43 ATOM 3730CB THR A 493 −16.845 26.234 −52.533 1.00 33.22 ATOM 3731 OG1 THR A 493−17.944 25.324 −52.431 1.00 38.55 ATOM 3732 CG2 THR A 493 −15.590 25.464−52.996 1.00 33.71 ATOM 3733 C THR A 493 −15.596 28.006 −51.254 1.0031.35 ATOM 3734 O THR A 493 −15.916 29.068 −51.795 1.00 31.58 ATOM 3735N PRO A 494 −14.390 27.815 −50.682 1.00 30.44 ATOM 3736 CA PRO A 494−13.464 28.947 −50.696 1.00 30.01 ATOM 3737 CB PRO A 494 −12.414 28.555−49.645 1.00 30.26 ATOM 3738 CG PRO A 494 −12.416 27.077 −49.658 1.0030.56 ATOM 3739 CD PRO A 494 −13.815 26.635 −49.997 1.00 30.85 ATOM 3740C PRO A 494 −12.809 29.089 −52.060 1.00 28.81 ATOM 3741 O PRO A 494−12.801 28.137 −52.834 1.00 28.82 ATOM 3742 N THR A 495 −12.260 30.258−52.352 1.00 28.43 ATOM 3743 CA THR A 495 −11.551 30.419 −53.623 1.0028.44 ATOM 3744 CB THR A 495 −11.885 31.748 −54.319 1.00 28.68 ATOM 3745OG1 THR A 495 −11.449 32.839 −53.500 1.00 30.39 ATOM 3746 CG2 THR A 495−13.383 31.858 −54.564 1.00 29.85 ATOM 3747 C THR A 495 −10.057 30.335−53.404 1.00 27.94 ATOM 3748 O THR A 495 −9.289 30.159 −54.352 1.0027.63 ATOM 3749 N SER A 496 −9.671 30.463 −52.139 1.00 27.51 ATOM 3750CA SER A 496 −8.279 30.492 −51.722 1.00 27.18 ATOM 3751 CB SER A 496−7.928 31.916 −51.329 1.00 27.72 ATOM 3752 OG SER A 496 −6.531 32.076−51.240 1.00 32.60 ATOM 3753 C SER A 496 −8.134 29.583 −50.501 1.0025.85 ATOM 3754 O SER A 496 −9.024 29.548 −49.634 1.00 25.10 ATOM 3755 NVAL A 497 −7.039 28.824 −50.430 1.00 24.43 ATOM 3756 CA VAL A 497 −6.80128.032 −49.209 1.00 22.17 ATOM 3757 CB VAL A 497 −7.281 26.511 −49.2901.00 23.00 ATOM 3758 CG1 VAL A 497 −6.224 25.445 −48.881 1.00 22.48 ATOM3759 CG2 VAL A 497 −8.049 26.161 −50.578 1.00 22.62 ATOM 3760 C VAL A497 −5.388 28.251 −48.672 1.00 21.13 ATOM 3761 O VAL A 497 −4.419 28.359−49.439 1.00 20.38 ATOM 3762 N ALA A 498 −5.302 28.395 −47.355 1.0019.70 ATOM 3763 CA ALA A 498 −4.020 28.576 −46.702 1.00 18.92 ATOM 3764CB ALA A 498 −4.226 29.126 −45.290 1.00 19.31 ATOM 3765 C ALA A 498−3.396 27.185 −46.655 1.00 18.67 ATOM 3766 O ALA A 498 −3.966 26.266−46.047 1.00 19.29 ATOM 3767 N VAL A 499 −2.252 27.021 −47.319 1.0017.23 ATOM 3768 CA VAL A 499 −1.551 25.735 −47.361 1.00 16.09 ATOM 3769CB VAL A 499 −1.165 25.347 −48.814 1.00 16.97 ATOM 3770 CG1 VAL A 499−0.403 23.984 −48.863 1.00 16.08 ATOM 3771 CG2 VAL A 499 −2.413 25.291−49.696 1.00 17.03 ATOM 3772 C VAL A 499 −0.306 25.841 −46.491 1.0015.95 ATOM 3773 O VAL A 499 0.604 26.607 −46.791 1.00 16.15 ATOM 3774 NTHR A 500 −0.279 25.085 −45.404 1.00 15.16 ATOM 3775 CA THR A 500 0.86325.116 −44.505 1.00 14.85 ATOM 3776 CB THR A 500 0.415 24.916 −43.0351.00 14.76 ATOM 3777 OG1 THR A 500 −0.403 26.022 −42.635 1.00 16.00 ATOM3778 CG2 THR A 500 1.639 24.856 −42.136 1.00 15.39 ATOM 3779 C THR A 5001.796 23.993 −44.932 1.00 14.99 ATOM 3780 O THR A 500 1.480 22.804−44.792 1.00 14.81 ATOM 3781 N PHE A 501 2.941 24.370 −45.481 1.00 14.71ATOM 3782 CA PHE A 501 3.981 23.411 −45.793 1.00 15.64 ATOM 3783 CB PHEA 501 4.943 23.964 −46.832 1.00 15.86 ATOM 3784 CG PHE A 501 4.28924.172 −48.168 1.00 18.38 ATOM 3785 CD1 PHE A 501 3.676 25.388 −48.4691.00 19.85 ATOM 3786 CE1 PHE A 501 3.052 25.581 −49.709 1.00 21.58 ATOM3787 CZ PHE A 501 3.015 24.547 −50.642 1.00 19.80 ATOM 3788 CE2 PHE A501 3.607 23.324 −50.356 1.00 21.69 ATOM 3789 CD2 PHE A 501 4.231 23.134−49.095 1.00 21.96 ATOM 3790 C PHE A 501 4.711 23.009 −44.536 1.00 15.81ATOM 3791 O PHE A 501 5.207 23.852 −43.804 1.00 16.78 ATOM 3792 N HIS A502 4.789 21.698 −44.317 1.00 14.85 ATOM 3793 CA HIS A 502 5.239 21.175−43.027 1.00 14.17 ATOM 3794 CB HIS A 502 3.987 20.565 −42.356 1.0014.85 ATOM 3795 CG HIS A 502 4.221 19.875 −41.054 1.00 13.69 ATOM 3796ND1 HIS A 502 4.819 18.637 −40.966 1.00 12.55 ATOM 3797 CE1 HIS A 5024.816 18.241 −39.702 1.00 15.76 ATOM 3798 NE2 HIS A 502 4.191 19.155−38.980 1.00 14.42 ATOM 3799 CD2 HIS A 502 3.797 20.183 −39.804 1.0014.92 ATOM 3800 C HIS A 502 6.317 20.161 −43.412 1.00 14.16 ATOM 3801 OHIS A 502 6.013 19.043 −43.824 1.00 13.85 ATOM 3802 N GLU A 503 7.57720.590 −43.352 1.00 13.63 ATOM 3803 CA GLU A 503 8.678 19.821 −43.9681.00 14.46 ATOM 3804 CB GLU A 503 9.434 20.712 −44.996 1.00 14.22 ATOM3805 CG GLU A 503 10.782 20.121 −45.524 1.00 16.31 ATOM 3806 CD GLU A503 10.620 18.973 −46.539 1.00 21.32 ATOM 3807 OE1 GLU A 503 11.52318.819 −47.393 1.00 21.21 ATOM 3808 OE2 GLU A 503 9.609 18.230 −46.5101.00 20.10 ATOM 3809 C GLU A 503 9.657 19.322 −42.917 1.00 14.22 ATOM3810 O GLU A 503 10.175 20.121 −42.131 1.00 15.31 ATOM 3811 N LEU A 5049.960 18.027 −42.927 1.00 14.92 ATOM 3812 CA LEU A 504 11.026 17.518−42.052 1.00 15.49 ATOM 3813 CB LEU A 504 10.658 16.147 −41.489 1.0016.33 ATOM 3814 CG LEU A 504 9.479 16.178 −40.498 1.00 17.19 ATOM 3815CD1 LEU A 504 8.922 14.753 −40.320 1.00 19.08 ATOM 3816 CD2 LEU A 5049.953 16.723 −39.198 1.00 17.28 ATOM 3817 C LEU A 504 12.318 17.428−42.846 1.00 16.59 ATOM 3818 O LEU A 504 12.403 16.656 −43.785 1.0016.72 ATOM 3819 N VAL A 505 13.317 18.201 −42.444 1.00 17.20 ATOM 3820CA VAL A 505 14.592 18.235 −43.154 1.00 19.16 ATOM 3821 CB VAL A 50514.548 19.141 −44.418 1.00 18.88 ATOM 3822 CG1 VAL A 505 14.028 20.539−44.090 1.00 19.28 ATOM 3823 CG2 VAL A 505 15.948 19.219 −45.095 1.0021.65 ATOM 3824 C VAL A 505 15.674 18.705 −42.188 1.00 20.00 ATOM 3825 OVAL A 505 15.595 19.785 −41.595 1.00 19.92 ATOM 3826 N SER A 506 16.68517.868 −42.011 1.00 21.73 ATOM 3827 CA SER A 506 17.761 18.216 −41.1041.00 23.33 ATOM 3828 CB SER A 506 18.570 16.974 −40.771 1.00 23.74 ATOM3829 OG SER A 506 19.583 17.320 −39.847 1.00 28.30 ATOM 3830 C SER A 50618.646 19.284 −41.759 1.00 23.03 ATOM 3831 O SER A 506 19.070 19.139−42.908 1.00 23.20 ATOM 3832 N THR A 507 18.868 20.371 −41.049 1.0024.01 ATOM 3833 CA THR A 507 19.685 21.464 −41.600 1.00 25.15 ATOM 3834CB THR A 507 18.845 22.725 −41.833 1.00 25.01 ATOM 3835 OG1 THR A 50718.104 23.015 −40.650 1.00 24.43 ATOM 3836 CG2 THR A 507 17.891 22.536−43.000 1.00 24.71 ATOM 3837 C THR A 507 20.795 21.812 −40.623 1.0027.09 ATOM 3838 O THR A 507 20.729 21.448 −39.451 1.00 26.15 ATOM 3839 NGLN A 508 21.798 22.536 −41.113 1.00 29.34 ATOM 3840 CA GLN A 508 22.91222.986 −40.272 1.00 32.54 ATOM 3841 CB GLN A 508 24.239 22.542 −40.8971.00 32.54 ATOM 3842 CG GLN A 508 24.369 21.010 −40.972 1.00 34.32 ATOM3843 CD GLN A 508 25.400 20.515 −41.991 1.00 36.23 ATOM 3844 OE1 GLN A508 26.283 19.700 −41.660 1.00 41.79 ATOM 3845 NE2 GLN A 508 25.27920.977 −43.242 1.00 40.42 ATOM 3846 C GLN A 508 22.827 24.502 −40.1001.00 33.06 ATOM 3847 O GLN A 508 22.136 25.178 −40.873 1.00 32.49 ATOM3848 N PHE A 509 23.494 25.037 −39.075 1.00 33.80 ATOM 3849 CA PHE A 50923.432 26.476 −38.782 1.00 35.03 ATOM 3850 CB PHE A 509 24.413 26.837−37.651 1.00 36.75 ATOM 3851 CG PHE A 509 24.481 28.315 −37.340 1.0039.07 ATOM 3852 CD1 PHE A 509 23.592 28.893 −36.428 1.00 41.58 ATOM 3853CE1 PHE A 509 23.642 30.265 −36.140 1.00 42.61 ATOM 3854 CZ PHE A 50924.603 31.073 −36.766 1.00 41.78 ATOM 3855 CE2 PHE A 509 25.507 30.503−37.678 1.00 42.48 ATOM 3856 CD2 PHE A 509 25.441 29.127 −37.955 1.0041.46 ATOM 3857 C PHE A 509 23.712 27.311 −40.040 1.00 34.58 ATOM 3858 OPHE A 509 24.614 26.990 −40.815 1.00 34.58 ATOM 3859 N GLY A 510 22.91228.355 −40.256 1.00 33.85 ATOM 3860 CA GLY A 510 23.101 29.241 −41.4071.00 33.22 ATOM 3861 C GLY A 510 22.352 28.826 −42.671 1.00 32.36 ATOM3862 O GLY A 510 22.369 29.545 −43.679 1.00 32.97 ATOM 3863 N GLN A 51121.705 27.663 −42.628 1.00 30.50 ATOM 3864 CA GLN A 511 20.885 27.217−43.745 1.00 29.02 ATOM 3865 CB GLN A 511 21.026 25.712 −43.931 1.0028.92 ATOM 3866 CG GLN A 511 22.436 25.276 −44.349 1.00 29.91 ATOM 3867CD GLN A 511 22.571 23.776 −44.439 1.00 31.36 ATOM 3868 OE1 GLN A 51121.760 23.036 −43.879 1.00 31.69 ATOM 3869 NE2 GLN A 511 23.590 23.309−45.160 1.00 30.72 ATOM 3870 C GLN A 511 19.418 27.619 −43.543 1.0027.82 ATOM 3871 O GLN A 511 18.928 27.695 −42.399 1.00 27.36 ATOM 3872 NTHR A 512 18.727 27.895 −44.650 1.00 25.92 ATOM 3873 CA THR A 512 17.30528.271 −44.613 1.00 24.51 ATOM 3874 CB THR A 512 17.126 29.763 −44.9941.00 24.95 ATOM 3875 OG1 THR A 512 17.769 30.580 −44.004 1.00 27.43 ATOM3876 CG2 THR A 512 15.653 30.151 −45.069 1.00 25.94 ATOM 3877 C THR A512 16.536 27.384 −45.600 1.00 23.09 ATOM 3878 O THR A 512 16.994 27.152−46.717 1.00 22.75 ATOM 3879 N VAL A 513 15.376 26.877 −45.200 1.0020.62 ATOM 3880 CA VAL A 513 14.593 26.074 −46.136 1.00 19.05 ATOM 3881CB VAL A 513 13.946 24.855 −45.428 1.00 19.18 ATOM 3882 CG1 VAL A 51313.041 24.064 −46.397 1.00 18.87 ATOM 3883 CG2 VAL A 513 15.042 23.938−44.895 1.00 20.56 ATOM 3884 C VAL A 513 13.536 26.979 −46.748 1.0017.98 ATOM 3885 O VAL A 513 12.910 27.768 −46.029 1.00 16.65 ATOM 3886 NLYS A 514 13.346 26.857 −48.063 1.00 17.91 ATOM 3887 CA LYS A 514 12.27927.583 −48.757 1.00 18.14 ATOM 3888 CB LYS A 514 12.845 28.712 −49.6381.00 17.66 ATOM 3889 CG LYS A 514 13.867 29.576 −48.945 1.00 19.26 ATOM3890 CD LYS A 514 14.197 30.839 −49.765 1.00 21.27 ATOM 3891 CE LYS A514 15.224 31.675 −49.001 1.00 26.06 ATOM 3892 NZ LYS A 514 15.46133.022 −49.626 1.00 28.70 ATOM 3893 C LYS A 514 11.494 26.621 −49.6251.00 18.22 ATOM 3894 O LYS A 514 11.949 25.502 −49.912 1.00 18.39 ATOM3895 N VAL A 515 10.304 27.037 −50.045 1.00 18.20 ATOM 3896 CA VAL A 5159.546 26.212 −50.980 1.00 19.00 ATOM 3897 CB VAL A 515 8.198 25.731−50.404 1.00 20.00 ATOM 3898 CG1 VAL A 515 7.403 26.904 −49.879 1.0021.01 ATOM 3899 CG2 VAL A 515 7.417 24.903 −51.447 1.00 20.10 ATOM 3900C VAL A 515 9.421 26.973 −52.302 1.00 18.89 ATOM 3901 O VAL A 515 9.07928.159 −52.317 1.00 18.67 ATOM 3902 N ALA A 516 9.781 26.295 −53.3901.00 19.87 ATOM 3903 CA ALA A 516 9.796 26.898 −54.732 1.00 20.38 ATOM3904 CB ALA A 516 11.177 26.768 −55.356 1.00 20.58 ATOM 3905 C ALA A 5168.789 26.110 −55.525 1.00 20.65 ATOM 3906 O ALA A 516 8.638 24.910−55.303 1.00 20.40 ATOM 3907 N GLY A 517 8.075 26.765 −56.430 1.00 20.80ATOM 3908 CA GLY A 517 7.092 26.039 −57.214 1.00 22.32 ATOM 3909 C GLY A517 6.536 26.853 −58.352 1.00 22.86 ATOM 3910 O GLY A 517 6.902 28.024−58.527 1.00 22.58 ATOM 3911 N ASN A 518 5.642 26.233 −59.116 1.00 24.66ATOM 3912 CA ASN A 518 5.201 26.817 −60.390 1.00 26.74 ATOM 3913 CB ASNA 518 4.670 25.754 −61.354 1.00 26.97 ATOM 3914 CG ASN A 518 3.38625.117 −60.872 1.00 31.69 ATOM 3915 OD1 ASN A 518 3.004 25.226 −59.6771.00 28.89 ATOM 3916 ND2 ASN A 518 2.707 24.419 −61.786 1.00 31.65 ATOM3917 C ASN A 518 4.199 27.937 −60.232 1.00 27.20 ATOM 3918 O ASN A 5184.154 28.822 −61.079 1.00 28.68 ATOM 3919 N ALA A 519 3.399 27.907−59.163 1.00 27.04 ATOM 3920 CA ALA A 519 2.424 28.978 −58.898 1.0026.47 ATOM 3921 CB ALA A 519 1.473 28.598 −57.747 1.00 27.02 ATOM 3922 CALA A 519 3.090 30.322 −58.629 1.00 26.35 ATOM 3923 O ALA A 519 4.22630.394 −58.135 1.00 25.27 ATOM 3924 N ALA A 520 2.369 31.394 −58.9541.00 26.25 ATOM 3925 CA ALA A 520 2.887 32.741 −58.784 1.00 26.77 ATOM3926 CB ALA A 520 1.872 33.775 −59.298 1.00 27.50 ATOM 3927 C ALA A 5203.250 33.004 −57.317 1.00 26.68 ATOM 3928 O ALA A 520 4.301 33.560−57.030 1.00 26.01 ATOM 3929 N ALA A 521 2.395 32.548 −56.399 1.00 26.75ATOM 3930 CA ALA A 521 2.628 32.712 −54.963 1.00 26.82 ATOM 3931 CB ALAA 521 1.395 32.251 −54.167 1.00 26.85 ATOM 3932 C ALA A 521 3.876 31.950−54.504 1.00 26.51 ATOM 3933 O ALA A 521 4.485 32.305 −53.494 1.00 26.63ATOM 3934 N LEU A 522 4.261 30.919 −55.259 1.00 26.79 ATOM 3935 CA LEU A522 5.452 30.113 −54.932 1.00 26.50 ATOM 3936 CB LEU A 522 5.185 28.626−55.155 1.00 26.64 ATOM 3937 CG LEU A 522 4.224 27.946 −54.169 1.0026.58 ATOM 3938 CD1 LEU A 522 4.049 26.489 −54.533 1.00 27.59 ATOM 3939CD2 LEU A 522 4.718 28.092 −52.730 1.00 28.08 ATOM 3940 C LEU A 5226.696 30.559 −55.709 1.00 26.54 ATOM 3941 O LEU A 522 7.779 29.987−55.547 1.00 25.56 ATOM 3942 N GLY A 523 6.518 31.575 −56.552 1.00 26.25ATOM 3943 CA GLY A 523 7.637 32.267 −57.199 1.00 26.16 ATOM 3944 C GLY A523 7.996 31.809 −58.607 1.00 26.84 ATOM 3945 O GLY A 523 9.029 32.227−59.152 1.00 25.81 ATOM 3946 N ASN A 524 7.162 30.946 −59.193 1.00 27.13ATOM 3947 CA ASN A 524 7.413 30.419 −60.539 1.00 27.74 ATOM 3948 CB ASNA 524 7.046 31.484 −61.591 1.00 28.43 ATOM 3949 CG ASN A 524 7.12330.960 −63.015 1.00 30.79 ATOM 3950 OD1 ASN A 524 6.856 29.780 −63.2851.00 30.80 ATOM 3951 ND2 ASN A 524 7.515 31.838 −63.936 1.00 33.61 ATOM3952 C ASN A 524 8.845 29.857 −60.710 1.00 28.44 ATOM 3953 O ASN A 5249.531 30.104 −61.720 1.00 27.82 ATOM 3954 N TRP A 525 9.280 29.111−59.693 1.00 27.99 ATOM 3955 CA TRP A 525 10.573 28.398 −59.659 1.0028.92 ATOM 3956 CB TRP A 525 10.787 27.507 −60.896 1.00 28.31 ATOM 3957CG TRP A 525 9.803 26.394 −61.060 1.00 27.68 ATOM 3958 CD1 TRP A 5258.902 26.247 −62.078 1.00 27.96 ATOM 3959 NE1 TRP A 525 8.166 25.106−61.907 1.00 27.55 ATOM 3960 CE2 TRP A 525 8.589 24.471 −60.762 1.0030.58 ATOM 3961 CD2 TRP A 525 9.609 25.277 −60.184 1.00 27.84 ATOM 3962CE3 TRP A 525 10.230 24.842 −59.001 1.00 26.50 ATOM 3963 CZ3 TRP A 5259.787 23.655 −58.411 1.00 27.55 ATOM 3964 CH2 TRP A 525 8.752 22.889−58.998 1.00 27.90 ATOM 3965 CZ2 TRP A 525 8.144 23.279 −60.168 1.0026.22 ATOM 3966 C TRP A 525 11.790 29.301 −59.452 1.00 29.66 ATOM 3967 OTRP A 525 12.921 28.804 −59.346 1.00 30.61 ATOM 3968 N SER A 526 11.57030.613 −59.380 1.00 30.33 ATOM 3969 CA SER A 526 12.645 31.536 −59.0041.00 31.13 ATOM 3970 CB SER A 526 12.213 32.993 −59.187 1.00 31.02 ATOM3971 OG SER A 526 13.166 33.838 −58.562 1.00 33.69 ATOM 3972 C SER A 52613.086 31.312 −57.560 1.00 31.29 ATOM 3973 O SER A 526 12.271 31.381−56.627 1.00 31.21 ATOM 3974 N THR A 527 14.373 31.049 −57.367 1.0031.34 ATOM 3975 CA THR A 527 14.880 30.794 −56.021 1.00 31.64 ATOM 3976CB THR A 527 16.259 30.098 −56.024 1.00 31.79 ATOM 3977 OG1 THR A 52717.217 30.931 −56.682 1.00 31.43 ATOM 3978 CG2 THR A 527 16.169 28.739−56.724 1.00 32.27 ATOM 3979 C THR A 527 14.911 32.045 −55.152 1.0031.99 ATOM 3980 O THR A 527 14.847 31.959 −53.922 1.00 32.36 ATOM 3981 NSER A 528 14.986 33.209 −55.787 1.00 31.79 ATOM 3982 CA SER A 528 14.92834.463 −55.054 1.00 32.02 ATOM 3983 CB SER A 528 15.517 35.615 −55.8851.00 32.70 ATOM 3984 OG SER A 528 14.712 35.882 −57.031 1.00 34.94 ATOM3985 C SER A 528 13.497 34.784 −54.579 1.00 31.23 ATOM 3986 O SER A 52813.330 35.435 −53.550 1.00 32.02 ATOM 3987 N ALA A 529 12.479 34.314−55.306 1.00 29.33 ATOM 3988 CA ALA A 529 11.093 34.506 −54.893 1.0027.60 ATOM 3989 CB ALA A 529 10.211 34.864 −56.086 1.00 27.34 ATOM 3990C ALA A 529 10.482 33.328 −54.112 1.00 26.40 ATOM 3991 O ALA A 529 9.31133.382 −53.754 1.00 26.54 ATOM 3992 N ALA A 530 11.268 32.286 −53.8421.00 25.12 ATOM 3993 CA ALA A 530 10.777 31.114 −53.096 1.00 24.19 ATOM3994 CB ALA A 530 11.855 30.063 −52.991 1.00 23.88 ATOM 3995 C ALA A 53010.336 31.555 −51.706 1.00 23.55 ATOM 3996 O ALA A 530 10.848 32.540−51.182 1.00 23.61 ATOM 3997 N VAL A 531 9.396 30.833 −51.110 1.00 22.18ATOM 3998 CA VAL A 531 8.851 31.248 −49.821 1.00 22.62 ATOM 3999 CB VALA 531 7.380 30.821 −49.677 1.00 22.81 ATOM 4000 CG1 VAL A 531 6.81531.335 −48.346 1.00 25.06 ATOM 4001 CG2 VAL A 531 6.551 31.353 −50.8861.00 25.38 ATOM 4002 C VAL A 531 9.659 30.646 −48.674 1.00 21.29 ATOM4003 O VAL A 531 9.768 29.425 −48.564 1.00 20.72 ATOM 4004 N ALA A 53210.215 31.493 −47.819 1.00 20.86 ATOM 4005 CA ALA A 532 11.008 30.999−46.698 1.00 20.26 ATOM 4006 CB ALA A 532 11.850 32.128 −46.084 1.0021.02 ATOM 4007 C ALA A 532 10.093 30.356 −45.646 1.00 20.51 ATOM 4008 OALA A 532 9.019 30.884 −45.337 1.00 20.05 ATOM 4009 N LEU A 533 10.51429.200 −45.129 1.00 19.00 ATOM 4010 CA LEU A 533 9.855 28.565 −43.9991.00 18.65 ATOM 4011 CB LEU A 533 9.901 27.029 −44.148 1.00 18.14 ATOM4012 CG LEU A 533 9.395 26.450 −45.483 1.00 19.25 ATOM 4013 CD1 LEU A533 9.385 24.923 −45.427 1.00 21.28 ATOM 4014 CD2 LEU A 533 8.030 26.980−45.894 1.00 18.58 ATOM 4015 C LEU A 533 10.541 29.014 −42.702 1.0018.95 ATOM 4016 O LEU A 533 11.622 29.648 −42.744 1.00 18.94 ATOM 4017 NASP A 534 9.905 28.715 −41.570 1.00 18.56 ATOM 4018 CA ASP A 534 10.38129.096 −40.238 1.00 18.36 ATOM 4019 CB ASP A 534 9.220 29.634 −39.3741.00 19.76 ATOM 4020 CG ASP A 534 8.757 30.992 −39.798 1.00 23.55 ATOM4021 OD1 ASP A 534 7.548 31.264 −39.659 1.00 26.14 ATOM 4022 OD2 ASP A534 9.600 31.774 −40.283 1.00 27.39 ATOM 4023 C ASP A 534 10.877 27.867−39.504 1.00 17.68 ATOM 4024 O ASP A 534 10.310 26.780 −39.667 1.0016.10 ATOM 4025 N ALA A 535 11.883 28.057 −38.654 1.00 17.05 ATOM 4026CA ALA A 535 12.405 26.950 −37.835 1.00 17.76 ATOM 4027 CB ALA A 53513.926 26.952 −37.832 1.00 17.96 ATOM 4028 C ALA A 535 11.872 27.027−36.403 1.00 17.82 ATOM 4029 O ALA A 535 12.482 26.490 −35.474 1.0018.36 ATOM 4030 N VAL A 536 10.745 27.706 −36.225 1.00 17.68 ATOM 4031CA VAL A 536 10.138 27.861 −34.898 1.00 18.65 ATOM 4032 CB VAL A 5368.824 28.719 −34.975 1.00 18.66 ATOM 4033 CG1 VAL A 536 7.805 28.123−35.971 1.00 19.98 ATOM 4034 CG2 VAL A 536 8.208 28.962 −33.570 1.0020.19 ATOM 4035 C VAL A 536 9.938 26.514 −34.155 1.00 18.51 ATOM 4036 OVAL A 536 10.124 26.437 −32.923 1.00 19.61 ATOM 4037 N ASN A 537 9.57025.468 −34.883 1.00 18.59 ATOM 4038 CA ASN A 537 9.344 24.154 −34.2611.00 19.07 ATOM 4039 CB ASN A 537 8.074 23.498 −34.816 1.00 19.28 ATOM4040 CG ASN A 537 6.800 24.252 −34.448 1.00 21.02 ATOM 4041 OD1 ASN A537 6.742 24.940 −33.435 1.00 24.12 ATOM 4042 ND2 ASN A 537 5.762 24.089−35.265 1.00 20.99 ATOM 4043 C ASN A 537 10.518 23.182 −34.445 1.0019.15 ATOM 4044 O ASN A 537 10.394 21.971 −34.196 1.00 18.60 ATOM 4045 NTYR A 538 11.653 23.699 −34.897 1.00 19.05 ATOM 4046 CA TYR A 538 12.76722.830 −35.234 1.00 20.32 ATOM 4047 CB TYR A 538 13.816 23.618 −36.0261.00 20.37 ATOM 4048 CG TYR A 538 14.916 22.747 −36.588 1.00 20.37 ATOM4049 CD1 TYR A 538 14.822 22.238 −37.886 1.00 20.39 ATOM 4050 CE1 TYR A538 15.853 21.436 −38.437 1.00 20.49 ATOM 4051 CZ TYR A 538 16.96121.137 −37.670 1.00 20.65 ATOM 4052 OH TYR A 538 17.946 20.341 −38.2181.00 21.53 ATOM 4053 CE2 TYR A 538 17.066 21.602 −36.361 1.00 22.05 ATOM4054 CD2 TYR A 538 16.043 22.418 −35.825 1.00 21.95 ATOM 4055 C TYR A538 13.436 22.209 −33.981 1.00 21.29 ATOM 4056 O TYR A 538 13.733 22.919−33.036 1.00 21.89 ATOM 4057 N ALA A 539 13.695 20.902 −34.014 1.0022.15 ATOM 4058 CA ALA A 539 14.646 20.258 −33.083 1.00 23.67 ATOM 4059CB ALA A 539 13.909 19.536 −31.976 1.00 23.94 ATOM 4060 C ALA A 53915.545 19.289 −33.849 1.00 24.35 ATOM 4061 O ALA A 539 15.117 18.698−34.833 1.00 23.63 ATOM 4062 N ASP A 540 16.793 19.118 −33.405 1.0025.69 ATOM 4063 CA ASP A 540 17.722 18.196 −34.099 1.00 27.42 ATOM 4064CB ASP A 540 19.044 18.051 −33.339 1.00 28.62 ATOM 4065 CG ASP A 54019.724 19.368 −33.140 1.00 33.80 ATOM 4066 OD1 ASP A 540 19.875 20.115−34.147 1.00 36.83 ATOM 4067 OD2 ASP A 540 20.080 19.663 −31.970 1.0040.32 ATOM 4068 C ASP A 540 17.150 16.818 −34.400 1.00 26.63 ATOM 4069 OASP A 540 17.386 16.277 −35.485 1.00 27.28 ATOM 4070 N ASN A 541 16.40316.247 −33.458 1.00 25.08 ATOM 4071 CA ASN A 541 15.827 14.922 −33.6871.00 24.03 ATOM 4072 CB ASN A 541 15.988 14.032 −32.441 1.00 25.14 ATOM4073 CG ASN A 541 15.337 14.623 −31.191 1.00 27.81 ATOM 4074 OD1 ASN A541 15.366 14.001 −30.118 1.00 31.57 ATOM 4075 ND2 ASN A 541 14.77115.824 −31.306 1.00 28.81 ATOM 4076 C ASN A 541 14.349 14.991 −34.1181.00 22.46 ATOM 4077 O ASN A 541 13.660 13.979 −34.172 1.00 22.35 ATOM4078 N HIS A 542 13.871 16.197 −34.403 1.00 19.85 ATOM 4079 CA HIS A 54212.580 16.354 −35.083 1.00 18.22 ATOM 4080 CB HIS A 542 11.426 16.392−34.062 1.00 16.89 ATOM 4081 CG HIS A 542 10.071 16.341 −34.699 1.0017.32 ATOM 4082 ND1 HIS A 542 9.211 17.417 −34.711 1.00 16.28 ATOM 4083CE1 HIS A 542 8.111 17.088 −35.371 1.00 14.64 ATOM 4084 NE2 HIS A 5428.217 15.834 −35.765 1.00 15.41 ATOM 4085 CD2 HIS A 542 9.435 15.340−35.358 1.00 15.14 ATOM 4086 C HIS A 542 12.662 17.650 −35.902 1.0017.48 ATOM 4087 O HIS A 542 12.198 18.698 −35.446 1.00 17.79 ATOM 4088 NPRO A 543 13.324 17.584 −37.083 1.00 17.00 ATOM 4089 CA PRO A 543 13.79718.752 −37.832 1.00 17.09 ATOM 4090 CB PRO A 543 14.948 18.164 −38.6771.00 16.57 ATOM 4091 CG PRO A 543 14.472 16.759 −38.994 1.00 18.22 ATOM4092 CD PRO A 543 13.676 16.321 −37.764 1.00 17.39 ATOM 4093 C PRO A 54312.718 19.435 −38.691 1.00 16.46 ATOM 4094 O PRO A 543 12.811 19.497−39.922 1.00 17.09 ATOM 4095 N LEU A 544 11.726 19.987 −38.009 1.0015.36 ATOM 4096 CA LEU A 544 10.534 20.535 −38.636 1.00 15.10 ATOM 4097CB LEU A 544 9.341 20.376 −37.672 1.00 15.29 ATOM 4098 CG LEU A 5447.968 20.927 −38.134 1.00 16.53 ATOM 4099 CD1 LEU A 544 7.524 20.364−39.494 1.00 15.92 ATOM 4100 CD2 LEU A 544 6.900 20.700 −37.062 1.0014.59 ATOM 4101 C LEU A 544 10.694 22.018 −39.025 1.00 15.09 ATOM 4102 OLEU A 544 11.037 22.851 −38.197 1.00 15.34 ATOM 4103 N TRP A 545 10.45622.298 −40.303 1.00 15.03 ATOM 4104 CA TRP A 545 10.327 23.637 −40.8431.00 15.36 ATOM 4105 CB TRP A 545 11.288 23.790 −42.023 1.00 15.40 ATOM4106 CG TRP A 545 12.758 23.921 −41.663 1.00 15.62 ATOM 4107 CD1 TRP A545 13.653 22.903 −41.384 1.00 16.85 ATOM 4108 NE1 TRP A 545 14.90623.437 −41.129 1.00 18.69 ATOM 4109 CE2 TRP A 545 14.837 24.803 −41.2461.00 17.78 ATOM 4110 CD2 TRP A 545 13.498 25.140 −41.584 1.00 17.01 ATOM4111 CE3 TRP A 545 13.163 26.488 −41.777 1.00 17.17 ATOM 4112 CZ3 TRP A545 14.165 27.456 −41.637 1.00 18.29 ATOM 4113 CH2 TRP A 545 15.48327.085 −41.295 1.00 17.22 ATOM 4114 CZ2 TRP A 545 15.835 25.767 −41.1111.00 19.09 ATOM 4115 C TRP A 545 8.907 23.832 −41.359 1.00 15.14 ATOM4116 O TRP A 545 8.327 22.933 −41.986 1.00 14.45 ATOM 4117 N ILE A 5468.362 25.025 −41.149 1.00 15.19 ATOM 4118 CA ILE A 546 6.938 25.244−41.428 1.00 16.51 ATOM 4119 CB ILE A 546 6.107 24.988 −40.130 1.0017.39 ATOM 4120 CG1 ILE A 546 4.615 24.852 −40.420 1.00 20.44 ATOM 4121CD1 ILE A 546 3.882 23.992 −39.392 1.00 23.59 ATOM 4122 CG2 ILE A 5466.391 26.064 −39.050 1.00 17.70 ATOM 4123 C ILE A 546 6.674 26.635−42.006 1.00 16.75 ATOM 4124 O ILE A 546 7.352 27.593 −41.647 1.00 15.81ATOM 4125 N ALA A 547 5.716 26.743 −42.925 1.00 16.88 ATOM 4126 CA ALA A547 5.197 28.057 −43.279 1.00 17.94 ATOM 4127 CB ALA A 547 6.222 28.893−43.931 1.00 21.49 ATOM 4128 C ALA A 547 4.009 27.919 −44.167 1.00 18.29ATOM 4129 O ALA A 547 3.727 26.828 −44.655 1.00 18.52 ATOM 4130 N THR A548 3.316 29.031 −44.362 1.00 17.99 ATOM 4131 CA THR A 548 1.970 29.017−44.919 1.00 18.72 ATOM 4132 CB THR A 548 0.929 29.419 −43.855 1.0018.65 ATOM 4133 OG1 THR A 548 1.000 28.500 −42.751 1.00 19.46 ATOM 4134CG2 THR A 548 −0.491 29.379 −44.438 1.00 18.79 ATOM 4135 C THR A 5481.865 29.960 −46.104 1.00 19.60 ATOM 4136 O THR A 548 2.347 31.090−46.040 1.00 19.83 ATOM 4137 N VAL A 549 1.227 29.485 −47.164 1.00 20.41ATOM 4138 CA VAL A 549 1.048 30.280 −48.389 1.00 22.36 ATOM 4139 CB VALA 549 1.944 29.722 −49.537 1.00 22.77 ATOM 4140 CG1 VAL A 549 1.71730.491 −50.845 1.00 25.80 ATOM 4141 CG2 VAL A 549 3.429 29.781 −49.1481.00 24.78 ATOM 4142 C VAL A 549 −0.399 30.119 −48.800 1.00 22.21 ATOM4143 O VAL A 549 −0.943 29.018 −48.719 1.00 21.56 ATOM 4144 N ASN A 550−1.028 31.211 −49.240 1.00 22.80 ATOM 4145 CA ASN A 550 −2.356 31.107−49.831 1.00 23.95 ATOM 4146 CB ASN A 550 −3.114 32.411 −49.649 1.0024.39 ATOM 4147 CG ASN A 550 −3.367 32.706 −48.201 1.00 27.42 ATOM 4148OD1 ASN A 550 −3.811 31.838 −47.462 1.00 28.69 ATOM 4149 ND2 ASN A 550−3.041 33.911 −47.771 1.00 31.89 ATOM 4150 C ASN A 550 −2.278 30.733−51.294 1.00 23.98 ATOM 4151 O ASN A 550 −1.598 31.400 −52.065 1.0024.73 ATOM 4152 N LEU A 551 −2.973 29.667 −51.662 1.00 24.24 ATOM 4153CA LEU A 551 −3.016 29.180 −53.020 1.00 24.78 ATOM 4154 CB LEU A 551−2.348 27.797 −53.135 1.00 25.00 ATOM 4155 CG LEU A 551 −0.858 27.721−52.787 1.00 25.19 ATOM 4156 CD1 LEU A 551 −0.356 26.284 −52.803 1.0027.45 ATOM 4157 CD2 LEU A 551 −0.018 28.613 −53.718 1.00 26.73 ATOM 4158C LEU A 551 −4.471 29.104 −53.488 1.00 25.46 ATOM 4159 O LEU A 551−5.393 29.018 −52.675 1.00 24.27 ATOM 4160 N GLU A 552 −4.661 29.148−54.804 1.00 26.15 ATOM 4161 CA GLU A 552 −6.004 29.165 −55.366 1.0028.20 ATOM 4162 CB GLU A 552 −5.955 29.639 −56.823 1.00 28.30 ATOM 4163CG GLU A 552 −7.326 29.739 −57.494 1.00 32.28 ATOM 4164 CD GLU A 552−7.250 30.281 −58.926 1.00 33.44 ATOM 4165 OE1 GLU A 552 −8.110 31.126−59.274 1.00 41.80 ATOM 4166 OE2 GLU A 552 −6.340 29.873 −59.695 1.0039.14 ATOM 4167 C GLU A 552 −6.610 27.768 −55.253 1.00 26.97 ATOM 4168 OGLU A 552 −5.979 26.783 −55.622 1.00 26.49 ATOM 4169 N ALA A 553 −7.82227.684 −54.723 1.00 27.21 ATOM 4170 CA ALA A 553 −8.502 26.399 −54.6031.00 27.89 ATOM 4171 CB ALA A 553 −9.876 26.574 −53.953 1.00 28.37 ATOM4172 C ALA A 553 −8.637 25.773 −55.979 1.00 28.57 ATOM 4173 O ALA A 553−8.900 26.477 −56.952 1.00 28.83 ATOM 4174 N GLY A 554 −8.438 24.465−56.064 1.00 28.44 ATOM 4175 CA GLY A 554 −8.556 23.753 −57.330 1.0029.66 ATOM 4176 C GLY A 554 −7.274 23.693 −58.145 1.00 30.04 ATOM 4177 OGLY A 554 −7.122 22.814 −59.000 1.00 30.33 ATOM 4178 N ASP A 555 −6.34724.606 −57.869 1.00 30.23 ATOM 4179 CA ASP A 555 −5.098 24.716 −58.6301.00 30.61 ATOM 4180 CB ASP A 555 −4.313 25.939 −58.161 1.00 30.85 ATOM4181 CG ASP A 555 −3.382 26.503 −59.236 1.00 34.49 ATOM 4182 OD1 ASP A555 −3.441 26.053 −60.407 1.00 37.19 ATOM 4183 OD2 ASP A 555 −2.57227.408 −58.901 1.00 36.59 ATOM 4184 C ASP A 555 −4.238 23.467 −58.4861.00 30.14 ATOM 4185 O ASP A 555 −4.156 22.882 −57.419 1.00 30.07 ATOM4186 N VAL A 556 −3.602 23.046 −59.572 1.00 29.55 ATOM 4187 CA VAL A 556−2.628 21.963 −59.492 1.00 28.74 ATOM 4188 CB VAL A 556 −2.732 20.987−60.680 1.00 29.35 ATOM 4189 CG1 VAL A 556 −1.666 19.877 −60.569 1.0028.99 ATOM 4190 CG2 VAL A 556 −4.125 20.365 −60.720 1.00 30.44 ATOM 4191C VAL A 556 −1.261 22.623 −59.448 1.00 28.04 ATOM 4192 O VAL A 556−0.869 23.336 −60.384 1.00 27.25 ATOM 4193 N VAL A 557 −0.544 22.389−58.352 1.00 26.81 ATOM 4194 CA VAL A 557 0.739 23.040 −58.100 1.0026.14 ATOM 4195 CB VAL A 557 0.690 23.859 −56.759 1.00 26.71 ATOM 4196CG1 VAL A 557 2.073 24.140 −56.219 1.00 27.82 ATOM 4197 CG2 VAL A 557−0.088 25.175 −56.952 1.00 27.34 ATOM 4198 C VAL A 557 1.856 21.999−58.092 1.00 25.64 ATOM 4199 O VAL A 557 1.646 20.845 −57.693 1.00 25.24ATOM 4200 N GLU A 558 3.035 22.409 −58.553 1.00 24.16 ATOM 4201 CA GLU A558 4.223 21.579 −58.516 1.00 24.38 ATOM 4202 CB GLU A 558 4.737 21.296−59.933 1.00 24.86 ATOM 4203 CG GLU A 558 4.064 20.108 −60.606 1.0026.34 ATOM 4204 CD GLU A 558 4.670 19.790 −61.962 1.00 27.68 ATOM 4205OE1 GLU A 558 5.917 19.684 −62.065 1.00 30.56 ATOM 4206 OE2 GLU A 5583.883 19.638 −62.915 1.00 32.45 ATOM 4207 C GLU A 558 5.262 22.337−57.730 1.00 22.54 ATOM 4208 O GLU A 558 5.389 23.550 −57.883 1.00 22.93ATOM 4209 N TYR A 559 5.992 21.640 −56.867 1.00 21.45 ATOM 4210 CA TYR A559 6.927 22.346 −55.995 1.00 19.96 ATOM 4211 CB TYR A 559 6.188 22.972−54.784 1.00 19.42 ATOM 4212 CG TYR A 559 5.624 21.952 −53.796 1.0018.65 ATOM 4213 CD1 TYR A 559 6.383 21.524 −52.703 1.00 18.64 ATOM 4214CE1 TYR A 559 5.887 20.595 −51.794 1.00 19.09 ATOM 4215 CZ TYR A 5594.614 20.090 −51.955 1.00 18.58 ATOM 4216 OH TYR A 559 4.135 19.160−51.056 1.00 20.55 ATOM 4217 CE2 TYR A 559 3.819 20.493 −53.024 1.0018.22 ATOM 4218 CD2 TYR A 559 4.335 21.438 −53.946 1.00 18.82 ATOM 4219C TYR A 559 8.066 21.445 −55.541 1.00 20.13 ATOM 4220 O TYR A 559 8.00820.215 −55.679 1.00 20.26 ATOM 4221 N LYS A 560 9.098 22.079 −54.9951.00 19.51 ATOM 4222 CA LYS A 560 10.208 21.379 −54.349 1.00 19.72 ATOM4223 CB LYS A 560 11.410 21.175 −55.282 1.00 19.66 ATOM 4224 CG LYS A560 11.390 19.870 −56.058 1.00 22.20 ATOM 4225 CD LYS A 560 12.76719.633 −56.714 1.00 24.46 ATOM 4226 CE LYS A 560 12.781 18.341 −57.5311.00 26.96 ATOM 4227 NZ LYS A 560 14.189 18.050 −57.980 1.00 26.97 ATOM4228 C LYS A 560 10.680 22.257 −53.234 1.00 18.68 ATOM 4229 O LYS A 56010.583 23.484 −53.318 1.00 19.68 ATOM 4230 N TYR A 561 11.240 21.640−52.206 1.00 17.87 ATOM 4231 CA TYR A 561 11.927 22.420 −51.187 1.0017.82 ATOM 4232 CB TYR A 561 11.921 21.690 −49.840 1.00 17.42 ATOM 4233CG TYR A 561 10.518 21.449 −49.346 1.00 16.12 ATOM 4234 CD1 TYR A 5619.831 20.276 −49.661 1.00 15.94 ATOM 4235 CE1 TYR A 561 8.511 20.062−49.199 1.00 15.79 ATOM 4236 CZ TYR A 561 7.897 21.050 −48.456 1.0015.89 ATOM 4237 OH TYR A 561 6.614 20.889 −47.981 1.00 17.17 ATOM 4238CE2 TYR A 561 8.557 22.224 −48.164 1.00 16.19 ATOM 4239 CD2 TYR A 5619.856 22.430 −48.625 1.00 17.57 ATOM 4240 C TYR A 561 13.360 22.650−51.607 1.00 18.63 ATOM 4241 O TYR A 561 13.963 21.786 −52.265 1.0018.40 ATOM 4242 N ILE A 562 13.904 23.792 −51.201 1.00 18.56 ATOM 4243CA ILE A 562 15.322 24.085 −51.434 1.00 20.18 ATOM 4244 CB ILE A 56215.524 25.247 −52.419 1.00 19.65 ATOM 4245 CG1 ILE A 562 14.837 26.520−51.896 1.00 21.64 ATOM 4246 CD1 ILE A 562 15.074 27.789 −52.741 1.0021.24 ATOM 4247 CG2 ILE A 562 15.017 24.829 −53.797 1.00 20.44 ATOM 4248C ILE A 562 15.971 24.446 −50.128 1.00 20.56 ATOM 4249 O ILE A 56215.316 24.956 −49.229 1.00 19.84 ATOM 4250 N ASN A 563 17.254 24.134−50.029 1.00 21.41 ATOM 4251 CA ASN A 563 18.076 24.467 −48.886 1.0022.99 ATOM 4252 CB ASN A 563 18.833 23.209 −48.435 1.00 22.69 ATOM 4253CG ASN A 563 19.629 23.433 −47.156 1.00 25.48 ATOM 4254 OD1 ASN A 56320.203 24.492 −46.965 1.00 28.81 ATOM 4255 ND2 ASN A 563 19.669 22.436−46.285 1.00 25.82 ATOM 4256 C ASN A 563 19.039 25.561 −49.372 1.0024.66 ATOM 4257 O ASN A 563 19.794 25.326 −50.323 1.00 24.16 ATOM 4258 NVAL A 564 18.977 26.749 −48.780 1.00 26.20 ATOM 4259 CA VAL A 564 19.87727.837 −49.206 1.00 28.74 ATOM 4260 CB VAL A 564 19.156 29.091 −49.8321.00 28.91 ATOM 4261 CG1 VAL A 564 19.461 30.408 −49.087 1.00 31.10 ATOM4262 CG2 VAL A 564 17.655 28.836 −50.079 1.00 28.92 ATOM 4263 C VAL A564 20.886 28.181 −48.122 1.00 29.56 ATOM 4264 O VAL A 564 20.538 28.320−46.954 1.00 29.10 ATOM 4265 N GLY A 565 22.150 28.266 −48.527 1.0032.02 ATOM 4266 CA GLY A 565 23.252 28.423 −47.577 1.00 34.92 ATOM 4267C GLY A 565 23.539 29.876 −47.248 1.00 37.47 ATOM 4268 O GLY A 56522.969 30.788 −47.871 1.00 37.66 ATOM 4269 N GLN A 566 24.419 30.098−46.267 1.00 39.85 ATOM 4270 CA GLN A 566 24.897 31.456 −45.926 1.0042.75 ATOM 4271 CB GLN A 566 26.054 31.398 −44.918 1.00 42.83 ATOM 4272CG GLN A 566 25.727 30.761 −43.565 1.00 44.99 ATOM 4273 CD GLN A 56626.940 30.689 −42.626 1.00 44.88 ATOM 4274 OE1 GLN A 566 27.972 30.089−42.958 1.00 47.67 ATOM 4275 NE2 GLN A 566 26.810 31.293 −41.441 1.0047.62 ATOM 4276 C GLN A 566 25.373 32.195 −47.181 1.00 43.30 ATOM 4277 OGLN A 566 25.052 33.365 −47.389 1.00 44.01 ATOM 4278 N ASP A 567 26.11831.479 −48.023 1.00 44.30 ATOM 4279 CA ASP A 567 26.739 32.029 −49.2361.00 44.62 ATOM 4280 CB ASP A 567 27.916 31.139 −49.650 1.00 45.13 ATOM4281 CG ASP A 567 27.492 29.702 −49.966 1.00 47.62 ATOM 4282 OD1 ASP A567 26.421 29.255 −49.485 1.00 48.73 ATOM 4283 OD2 ASP A 567 28.24529.010 −50.693 1.00 50.47 ATOM 4284 C ASP A 567 25.776 32.197 −50.4211.00 44.04 ATOM 4285 O ASP A 567 26.196 32.575 −51.522 1.00 44.36 ATOM4286 N GLY A 568 24.497 31.899 −50.205 1.00 42.85 ATOM 4287 CA GLY A 56823.488 32.045 −51.247 1.00 41.38 ATOM 4288 C GLY A 568 23.359 30.851−52.177 1.00 40.41 ATOM 4289 O GLY A 568 22.496 30.854 −53.054 1.0040.62 ATOM 4290 N SER A 569 24.195 29.827 −51.990 1.00 39.02 ATOM 4291CA SER A 569 24.137 28.623 −52.827 1.00 37.72 ATOM 4292 CB SER A 56925.365 27.746 −52.600 1.00 38.07 ATOM 4293 OG SER A 569 25.454 27.359−51.238 1.00 39.18 ATOM 4294 C SER A 569 22.868 27.819 −52.540 1.0036.72 ATOM 4295 O SER A 569 22.474 27.672 −51.382 1.00 36.47 ATOM 4296 NVAL A 570 22.222 27.313 −53.583 1.00 35.25 ATOM 4297 CA VAL A 570 20.98826.558 −53.365 1.00 34.26 ATOM 4298 CB VAL A 570 19.709 27.243 −53.9871.00 34.42 ATOM 4299 CG1 VAL A 570 18.992 26.358 −55.020 1.00 35.11 ATOM4300 CG2 VAL A 570 20.010 28.651 −54.506 1.00 35.12 ATOM 4301 C VAL A570 21.113 25.080 −53.718 1.00 33.29 ATOM 4302 O VAL A 570 21.735 24.694−54.714 1.00 32.88 ATOM 4303 N THR A 571 20.515 24.261 −52.864 1.0031.66 ATOM 4304 CA THR A 571 20.480 22.825 −53.021 1.00 30.87 ATOM 4305CB THR A 571 21.016 22.146 −51.752 1.00 30.96 ATOM 4306 OG1 THR A 57122.311 22.686 −51.442 1.00 33.18 ATOM 4307 CG2 THR A 571 21.117 20.637−51.935 1.00 30.95 ATOM 4308 C THR A 571 19.018 22.473 −53.210 1.0029.72 ATOM 4309 O THR A 571 18.186 22.832 −52.373 1.00 28.84 ATOM 4310 NTRP A 572 18.697 21.846 −54.337 1.00 29.01 ATOM 4311 CA TRP A 572 17.33121.388 −54.589 1.00 28.49 ATOM 4312 CB TRP A 572 17.004 21.367 −56.0861.00 28.99 ATOM 4313 CG TRP A 572 16.950 22.690 −56.739 1.00 29.65 ATOM4314 CD1 TRP A 572 18.014 23.419 −57.217 1.00 30.67 ATOM 4315 NE1 TRP A572 17.564 24.603 −57.769 1.00 31.84 ATOM 4316 CE2 TRP A 572 16.19624.655 −57.668 1.00 30.45 ATOM 4317 CD2 TRP A 572 15.770 23.464 −57.0281.00 30.30 ATOM 4318 CE3 TRP A 572 14.398 23.274 −56.791 1.00 29.43 ATOM4319 CZ3 TRP A 572 13.502 24.266 −57.205 1.00 30.24 ATOM 4320 CH2 TRP A572 13.959 25.437 −57.846 1.00 30.31 ATOM 4321 CZ2 TRP A 572 15.29825.649 −58.083 1.00 29.71 ATOM 4322 C TRP A 572 17.205 19.991 −54.0311.00 28.21 ATOM 4323 O TRP A 572 18.168 19.212 −54.060 1.00 27.50 ATOM4324 N GLU A 573 16.033 19.647 −53.499 1.00 27.69 ATOM 4325 CA GLU A 57315.819 18.251 −53.123 1.00 27.17 ATOM 4326 CB GLU A 573 14.586 18.074−52.222 1.00 27.18 ATOM 4327 CG GLU A 573 13.287 18.406 −52.901 1.0026.04 ATOM 4328 CD GLU A 573 12.059 18.111 −52.028 1.00 26.20 ATOM 4329OE1 GLU A 573 12.112 17.224 −51.141 1.00 25.84 ATOM 4330 OE2 GLU A 57311.032 18.764 −52.264 1.00 22.24 ATOM 4331 C GLU A 573 15.725 17.419−54.405 1.00 27.91 ATOM 4332 O GLU A 573 15.498 17.957 −55.497 1.0026.94 ATOM 4333 N SER A 574 15.907 16.108 −54.267 1.00 28.48 ATOM 4334CA SER A 574 15.880 15.201 −55.410 1.00 29.59 ATOM 4335 CB SER A 57416.296 13.805 −54.975 1.00 29.73 ATOM 4336 OG SER A 574 17.609 13.875−54.449 1.00 32.74 ATOM 4337 C SER A 574 14.526 15.134 −56.095 1.0029.70 ATOM 4338 O SER A 574 13.500 15.482 −55.513 1.00 29.12 ATOM 4339 NASP A 575 14.544 14.669 −57.339 1.00 29.54 ATOM 4340 CA ASP A 575 13.33714.435 −58.109 1.00 29.98 ATOM 4341 CB ASP A 575 13.705 14.000 −59.5341.00 30.69 ATOM 4342 CG ASP A 575 14.324 15.125 −60.331 1.00 33.96 ATOM4343 OD1 ASP A 575 14.056 16.299 −59.997 1.00 36.25 ATOM 4344 OD2 ASP A575 15.083 14.846 −61.290 1.00 37.94 ATOM 4345 C ASP A 575 12.519 13.358−57.428 1.00 28.93 ATOM 4346 O ASP A 575 13.050 12.633 −56.600 1.0028.34 ATOM 4347 N PRO A 576 11.217 13.267 −57.760 1.00 28.58 ATOM 4348CA PRO A 576 10.469 14.173 −58.650 1.00 27.92 ATOM 4349 CB PRO A 5769.319 13.294 −59.131 1.00 28.52 ATOM 4350 CG PRO A 576 9.053 12.378−57.954 1.00 28.29 ATOM 4351 CD PRO A 576 10.377 12.159 −57.267 1.0028.76 ATOM 4352 C PRO A 576 9.894 15.397 −57.938 1.00 27.25 ATOM 4353 OPRO A 576 9.887 15.452 −56.703 1.00 28.13 ATOM 4354 N ASN A 577 9.39416.360 −58.707 1.00 25.62 ATOM 4355 CA ASN A 577 8.612 17.449 −58.1291.00 24.83 ATOM 4356 CB ASN A 577 8.013 18.336 −59.224 1.00 24.90 ATOM4357 CG ASN A 577 9.055 19.184 −59.913 1.00 25.61 ATOM 4358 OD1 ASN A577 10.176 19.321 −59.423 1.00 25.83 ATOM 4359 ND2 ASN A 577 8.69319.756 −61.060 1.00 25.07 ATOM 4360 C ASN A 577 7.466 16.868 −57.3221.00 24.22 ATOM 4361 O ASN A 577 6.949 15.798 −57.672 1.00 23.69 ATOM4362 N HIS A 578 7.057 17.562 −56.259 1.00 23.20 ATOM 4363 CA HIS A 5785.830 17.179 −55.570 1.00 22.96 ATOM 4364 CB HIS A 578 5.734 17.844−54.200 1.00 22.09 ATOM 4365 CG HIS A 578 6.874 17.538 −53.285 1.0021.80 ATOM 4366 ND1 HIS A 578 6.809 16.558 −52.318 1.00 21.62 ATOM 4367CE1 HIS A 578 7.948 16.530 −51.645 1.00 21.36 ATOM 4368 NE2 HIS A 5788.743 17.465 −52.133 1.00 20.16 ATOM 4369 CD2 HIS A 578 8.096 18.109−53.160 1.00 19.78 ATOM 4370 C HIS A 578 4.697 17.707 −56.429 1.00 23.58ATOM 4371 O HIS A 578 4.814 18.794 −56.976 1.00 23.64 ATOM 4372 N THR A579 3.603 16.955 −56.534 1.00 23.98 ATOM 4373 CA THR A 579 2.426 17.448−57.254 1.00 25.34 ATOM 4374 CB THR A 579 2.092 16.568 −58.477 1.0026.08 ATOM 4375 OG1 THR A 579 3.162 16.672 −59.429 1.00 29.14 ATOM 4376CG2 THR A 579 0.749 16.979 −59.126 1.00 26.14 ATOM 4377 C THR A 5791.259 17.480 −56.291 1.00 25.05 ATOM 4378 O THR A 579 0.977 16.487−55.629 1.00 25.73 ATOM 4379 N TYR A 580 0.591 18.619 −56.213 1.00 25.23ATOM 4380 CA TYR A 580 −0.450 18.802 −55.211 1.00 25.68 ATOM 4381 CB TYRA 580 0.098 19.556 −53.976 1.00 25.88 ATOM 4382 CG TYR A 580 −0.93119.763 −52.866 1.00 26.21 ATOM 4383 CD1 TYR A 580 −1.284 21.048 −52.4291.00 26.22 ATOM 4384 CE1 TYR A 580 −2.256 21.233 −51.399 1.00 27.53 ATOM4385 CZ TYR A 580 −2.860 20.111 −50.841 1.00 27.08 ATOM 4386 OH TYR A580 −3.806 20.207 −49.844 1.00 27.88 ATOM 4387 CE2 TYR A 580 −2.51018.841 −51.264 1.00 26.97 ATOM 4388 CD2 TYR A 580 −1.562 18.671 −52.2761.00 26.29 ATOM 4389 C TYR A 580 −1.634 19.523 −55.828 1.00 25.65 ATOM4390 O TYR A 580 −1.490 20.596 −56.403 1.00 25.29 ATOM 4391 N THR A 581−2.813 18.915 −55.732 1.00 25.95 ATOM 4392 CA THR A 581 −4.015 19.629−56.117 1.00 25.78 ATOM 4393 CB THR A 581 −5.016 18.700 −56.806 1.0026.75 ATOM 4394 OG1 THR A 581 −4.332 18.000 −57.855 1.00 26.57 ATOM 4395CG2 THR A 581 −6.189 19.498 −57.397 1.00 27.62 ATOM 4396 C THR A 581−4.627 20.285 −54.874 1.00 25.36 ATOM 4397 O THR A 581 −5.024 19.595−53.935 1.00 25.22 ATOM 4398 N VAL A 582 −4.685 21.615 −54.880 1.0024.54 ATOM 4399 CA VAL A 582 −5.255 22.382 −53.777 1.00 24.15 ATOM 4400CB VAL A 582 −5.006 23.915 −53.953 1.00 24.21 ATOM 4401 CG1 VAL A 582−5.472 24.700 −52.744 1.00 23.87 ATOM 4402 CG2 VAL A 582 −3.514 24.218−54.219 1.00 25.33 ATOM 4403 C VAL A 582 −6.759 22.063 −53.706 1.0024.32 ATOM 4404 O VAL A 582 −7.478 22.204 −54.700 1.00 23.26 ATOM 4405 NPRO A 583 −7.236 21.587 −52.546 1.00 24.10 ATOM 4406 CA PRO A 583 −8.66521.230 −52.476 1.00 24.34 ATOM 4407 CB PRO A 583 −8.865 20.763 −51.0221.00 24.33 ATOM 4408 CG PRO A 583 −7.516 20.538 −50.468 1.00 25.16 ATOM4409 CD PRO A 583 −6.508 21.310 −51.294 1.00 24.72 ATOM 4410 C PRO A 583−9.597 22.404 −52.768 1.00 24.50 ATOM 4411 O PRO A 583 −9.262 23.558−52.487 1.00 23.93 ATOM 4412 N ALA A 584 −10.756 22.104 −53.350 1.0024.61 ATOM 4413 CA ALA A 584 −11.817 23.084 −53.477 1.00 24.77 ATOM 4414CB ALA A 584 −12.065 23.439 −54.943 1.00 25.29 ATOM 4415 C ALA A 584−13.036 22.434 −52.847 1.00 24.94 ATOM 4416 O ALA A 584 −13.922 21.932−53.537 1.00 25.03 ATOM 4417 N VAL A 585 −13.052 22.406 −51.517 1.0024.24 ATOM 4418 CA VAL A 585 −14.075 21.673 −50.776 1.00 23.75 ATOM 4419CB VAL A 585 −13.465 20.452 −50.029 1.00 24.50 ATOM 4420 CG1 VAL A 585−14.515 19.770 −49.151 1.00 24.48 ATOM 4421 CG2 VAL A 585 −12.863 19.447−51.026 1.00 25.32 ATOM 4422 C VAL A 585 −14.707 22.639 −49.781 1.0023.20 ATOM 4423 O VAL A 585 −13.999 23.347 −49.065 1.00 22.13 ATOM 4424N ALA A 586 −16.044 22.679 −49.739 1.00 22.43 ATOM 4425 CA ALA A 586−16.749 23.546 −48.804 1.00 21.79 ATOM 4426 CB ALA A 586 −18.240 23.212−48.820 1.00 22.19 ATOM 4427 C ALA A 586 −16.160 23.324 −47.389 1.0021.57 ATOM 4428 O ALA A 586 −15.954 22.180 −46.990 1.00 20.89 ATOM 4429N CYS A 587 −15.872 24.414 −46.679 1.00 21.59 ATOM 4430 CA CYS A 587−15.388 24.379 −45.268 1.00 21.68 ATOM 4431 CB CYS A 587 −16.131 23.323−44.441 1.00 22.08 ATOM 4432 SG CYS A 587 −17.952 23.374 −44.507 1.0023.60 ATOM 4433 C CYS A 587 −13.886 24.129 −45.094 1.00 21.27 ATOM 4434O CYS A 587 −13.386 24.225 −43.980 1.00 21.08 ATOM 4435 N VAL A 588−13.178 23.780 −46.170 1.00 20.53 ATOM 4436 CA VAL A 588 −11.742 23.499−46.085 1.00 20.52 ATOM 4437 CB VAL A 588 −11.351 22.268 −46.958 1.0020.47 ATOM 4438 CG1 VAL A 588 −9.846 21.959 −46.844 1.00 20.87 ATOM 4439CG2 VAL A 588 −12.163 21.042 −46.549 1.00 20.51 ATOM 4440 C VAL A 588−10.949 24.731 −46.504 1.00 20.59 ATOM 4441 O VAL A 588 −10.699 24.950−47.705 1.00 21.88 ATOM 4442 N THR A 589 −10.533 25.522 −45.528 1.0019.56 ATOM 4443 CA THR A 589 −9.903 26.807 −45.795 1.00 19.48 ATOM 4444CB THR A 589 −10.595 27.914 −44.988 1.00 20.13 ATOM 4445 OG1 THR A 589−10.527 27.565 −43.592 1.00 21.49 ATOM 4446 CG2 THR A 589 −12.085 28.018−45.410 1.00 20.03 ATOM 4447 C THR A 589 −8.424 26.819 −45.427 1.0019.42 ATOM 4448 O THR A 589 −7.694 27.767 −45.743 1.00 18.66 ATOM 4449 NGLN A 590 −7.995 25.772 −44.734 1.00 19.62 ATOM 4450 CA GLN A 590 −6.60625.629 −44.317 1.00 20.20 ATOM 4451 CB GLN A 590 −6.359 26.261 −42.9391.00 21.06 ATOM 4452 CG GLN A 590 −4.950 25.956 −42.410 1.00 27.00 ATOM4453 CD GLN A 590 −4.184 27.189 −41.989 1.00 33.74 ATOM 4454 OE1 GLN A590 −4.771 28.196 −41.611 1.00 37.22 ATOM 4455 NE2 GLN A 590 −2.85527.118 −42.066 1.00 36.77 ATOM 4456 C GLN A 590 −6.247 24.159 −44.2951.00 19.00 ATOM 4457 O GLN A 590 −7.004 23.335 −43.771 1.00 18.70 ATOM4458 N VAL A 591 −5.113 23.811 −44.904 1.00 17.70 ATOM 4459 CA VAL A 591−4.682 22.404 −44.940 1.00 17.15 ATOM 4460 CB VAL A 591 −4.843 21.750−46.330 1.00 17.82 ATOM 4461 CG1 VAL A 591 −6.316 21.701 −46.744 1.0018.11 ATOM 4462 CG2 VAL A 591 −3.970 22.470 −47.390 1.00 17.60 ATOM 4463C VAL A 591 −3.213 22.360 −44.551 1.00 17.42 ATOM 4464 O VAL A 591−2.531 23.377 −44.638 1.00 17.32 ATOM 4465 N VAL A 592 −2.731 21.206−44.090 1.00 17.26 ATOM 4466 CA VAL A 592 −1.291 21.092 −43.887 1.0017.03 ATOM 4467 CB VAL A 592 −0.762 21.198 −42.365 1.00 18.70 ATOM 4468CG1 VAL A 592 0.335 20.217 −41.930 1.00 18.75 ATOM 4469 CG2 VAL A 592−1.810 21.731 −41.315 1.00 15.36 ATOM 4470 C VAL A 592 −0.736 19.951−44.730 1.00 16.99 ATOM 4471 O VAL A 592 −1.318 18.862 −44.828 1.0016.23 ATOM 4472 N LYS A 593 0.357 20.253 −45.403 1.00 15.38 ATOM 4473 CALYS A 593 0.953 19.302 −46.293 1.00 16.27 ATOM 4474 CB LYS A 593 1.30120.010 −47.616 1.00 16.69 ATOM 4475 CG LYS A 593 1.835 19.096 −48.6941.00 20.55 ATOM 4476 CD LYS A 593 0.791 18.101 −49.203 1.00 24.73 ATOM4477 CE LYS A 593 1.330 17.311 −50.409 1.00 27.26 ATOM 4478 NZ LYS A 5932.395 16.299 −50.074 1.00 28.37 ATOM 4479 C LYS A 593 2.209 18.783−45.588 1.00 16.01 ATOM 4480 O LYS A 593 3.175 19.525 −45.427 1.00 15.12ATOM 4481 N GLU A 594 2.195 17.519 −45.175 1.00 15.82 ATOM 4482 CA GLU A594 3.308 16.969 −44.407 1.00 16.23 ATOM 4483 CB GLU A 594 2.798 16.017−43.317 1.00 16.26 ATOM 4484 CG GLU A 594 1.866 16.732 −42.299 1.0016.62 ATOM 4485 CD GLU A 594 1.727 15.949 −40.991 1.00 18.94 ATOM 4486OE1 GLU A 594 1.267 14.778 −41.024 1.00 21.31 ATOM 4487 OE2 GLU A 5942.107 16.507 −39.940 1.00 16.43 ATOM 4488 C GLU A 594 4.286 16.245−45.323 1.00 17.34 ATOM 4489 O GLU A 594 3.973 15.177 −45.852 1.00 17.78ATOM 4490 N ASP A 595 5.463 16.833 −45.487 1.00 17.05 ATOM 4491 CA ASP A595 6.481 16.326 −46.405 1.00 17.21 ATOM 4492 CB ASP A 595 6.823 17.379−47.475 1.00 16.63 ATOM 4493 CG ASP A 595 5.678 17.619 −48.455 1.0017.91 ATOM 4494 OD1 ASP A 595 5.023 16.631 −48.857 1.00 20.73 ATOM 4495OD2 ASP A 595 5.434 18.795 −48.844 1.00 18.08 ATOM 4496 C ASP A 5957.734 15.955 −45.631 1.00 17.47 ATOM 4497 O ASP A 595 7.915 16.375−44.492 1.00 16.44 ATOM 4498 N THR A 596 8.598 15.162 −46.277 1.00 18.11ATOM 4499 CA THR A 596 9.917 14.835 −45.747 1.00 18.85 ATOM 4500 CB THRA 596 9.991 13.390 −45.188 1.00 19.58 ATOM 4501 OG1 THR A 596 9.05713.248 −44.116 1.00 20.97 ATOM 4502 CG2 THR A 596 11.385 13.124 −44.5981.00 20.94 ATOM 4503 C THR A 596 10.895 14.978 −46.914 1.00 19.34 ATOM4504 O THR A 596 10.588 14.531 −48.024 1.00 19.05 ATOM 4505 N TRP A 59712.050 15.581 −46.631 1.00 20.24 ATOM 4506 CA TRP A 597 13.074 15.921−47.633 1.00 21.94 ATOM 4507 CB TRP A 597 14.325 16.453 −46.940 1.0022.34 ATOM 4508 CG TRP A 597 15.445 16.854 −47.882 1.00 23.75 ATOM 4509CD1 TRP A 597 16.509 16.079 −48.275 1.00 25.08 ATOM 4510 NE1 TRP A 59717.327 16.801 −49.138 1.00 24.85 ATOM 4511 CE2 TRP A 597 16.802 18.059−49.300 1.00 25.25 ATOM 4512 CD2 TRP A 597 15.611 18.128 −48.527 1.0024.09 ATOM 4513 CE3 TRP A 597 14.875 19.325 −48.519 1.00 24.91 ATOM 4514CZ3 TRP A 597 15.334 20.401 −49.262 1.00 23.38 ATOM 4515 CH2 TRP A 59716.520 20.299 −50.028 1.00 25.14 ATOM 4516 CZ2 TRP A 597 17.265 19.137−50.053 1.00 22.49 ATOM 4517 C TRP A 597 13.424 14.708 −48.473 1.0023.42 ATOM 4518 O TRP A 597 13.675 13.635 −47.939 1.00 22.37 ATOM 4519 NGLN A 598 13.409 14.904 −49.788 1.00 25.26 ATOM 4520 CA GLN A 598 13.69813.850 −50.755 1.00 27.05 ATOM 4521 CB GLN A 598 12.936 14.124 −52.0521.00 26.51 ATOM 4522 CG GLN A 598 11.418 13.948 −51.895 1.00 26.10 ATOM4523 CD GLN A 598 10.642 14.209 −53.156 1.00 26.76 ATOM 4524 OE1 GLN A598 11.194 14.620 −54.175 1.00 27.68 ATOM 4525 NE2 GLN A 598 9.34013.990 −53.095 1.00 25.96 ATOM 4526 C GLN A 598 15.204 13.787 −50.9771.00 29.21 ATOM 4527 O GLN A 598 15.794 14.694 −51.574 1.00 28.61 ATOM4528 N SER A 599 15.818 12.722 −50.453 1.00 32.41 ATOM 4529 CA SER A 59917.273 12.530 −50.498 1.00 35.70 ATOM 4530 CB SER A 599 17.747 11.698−49.302 1.00 35.61 ATOM 4531 OG SER A 599 17.374 12.296 −48.072 1.0039.62 ATOM 4532 C SER A 599 17.703 11.831 −51.785 1.00 36.66 ATOM 4533 OSER A 599 16.916 11.145 −52.433 1.00 37.44 ATOM 4534 OXT SER A 59918.863 11.922 −52.194 1.00 38.18 ATOM 4535 C1 MAN A 601 −3.602 −3.018−46.412 1.00 102.64 ATOM 4536 C2 MAN A 601 −4.584 −2.109 −47.156 1.00102.73 ATOM 4537 O2 MAN A 601 −3.951 −1.548 −48.288 1.00 102.91 ATOM4538 C3 MAN A 601 −5.867 −2.845 −47.570 1.00 102.38 ATOM 4539 O3 MAN A601 −6.544 −2.112 −48.566 1.00 102.32 ATOM 4540 C4 MAN A 601 −5.640−4.269 −48.082 1.00 102.18 ATOM 4541 O4 MAN A 601 −6.860 −4.967 −47.9841.00 101.76 ATOM 4542 C5 MAN A 601 −4.561 −5.018 −47.298 1.00 102.40ATOM 4543 C6 MAN A 601 −4.172 −6.307 −48.010 1.00 102.48 ATOM 4544 O6MAN A 601 −3.156 −6.957 −47.280 1.00 102.80 ATOM 4545 O5 MAN A 601−3.400 −4.222 −47.131 1.00 102.71 ATOM 4546 C1 MAN A 602 −29.428 −4.974−42.477 1.00 77.32 ATOM 4547 C2 MAN A 602 −28.973 −6.434 −42.405 1.0077.44 ATOM 4548 O2 MAN A 602 −30.120 −7.253 −42.347 1.00 77.72 ATOM 4549C3 MAN A 602 −28.044 −6.835 −43.565 1.00 77.20 ATOM 4550 O3 MAN A 602−27.940 −8.239 −43.664 1.00 76.96 ATOM 4551 C4 MAN A 602 −28.487 −6.260−44.909 1.00 77.22 ATOM 4552 O4 MAN A 602 −27.471 −6.474 −45.862 1.0076.90 ATOM 4553 C5 MAN A 602 −28.766 −4.766 −44.768 1.00 77.47 ATOM 4554C6 MAN A 602 −29.185 −4.115 −46.081 1.00 77.84 ATOM 4555 O6 MAN A 602−28.163 −3.228 −46.483 1.00 78.24 ATOM 4556 O5 MAN A 602 −29.768 −4.562−43.790 1.00 77.46 ATOM 4557 C1 MAN A 603 −18.689 25.235 −53.677 1.0047.04 ATOM 4558 C2 MAN A 603 −20.074 24.872 −53.114 1.00 51.09 ATOM 4559O2 MAN A 603 −21.044 25.065 −54.120 1.00 52.42 ATOM 4560 C3 MAN A 603−20.141 23.420 −52.620 1.00 51.78 ATOM 4561 O3 MAN A 603 −21.465 23.079−52.262 1.00 53.36 ATOM 4562 C4 MAN A 603 −19.602 22.466 −53.686 1.0051.72 ATOM 4563 O4 MAN A 603 −19.615 21.142 −53.209 1.00 51.94 ATOM 4564C5 MAN A 603 −18.179 22.911 −54.021 1.00 51.66 ATOM 4565 C6 MAN A 603−17.421 21.906 −54.892 1.00 53.80 ATOM 4566 O6 MAN A 603 −17.915 21.885−56.214 1.00 55.49 ATOM 4567 O5 MAN A 603 −18.217 24.223 −54.581 1.0049.62 ATOM 4568 C1 MAN A 605 −4.678 15.117 −57.896 1.00 58.79 ATOM 4569C2 MAN A 605 −3.360 15.555 −58.538 1.00 58.65 ATOM 4570 O2 MAN A 605−2.564 14.412 −58.722 1.00 59.38 ATOM 4571 C3 MAN A 605 −3.570 16.269−59.878 1.00 58.70 ATOM 4572 O3 MAN A 605 −2.523 15.985 −60.778 1.0059.27 ATOM 4573 C4 MAN A 605 −4.915 15.892 −60.491 1.00 58.73 ATOM 4574O4 MAN A 605 −5.084 16.538 −61.730 1.00 59.62 ATOM 4575 C5 MAN A 605−6.054 16.284 −59.547 1.00 58.90 ATOM 4576 C6 MAN A 605 −7.370 15.612−59.932 1.00 58.75 ATOM 4577 O6 MAN A 605 −7.255 14.219 −59.738 1.0059.42 ATOM 4578 O5 MAN A 605 −5.730 16.034 −58.173 1.00 58.30 ATOM 4579C1 MAN A 606 −10.273 28.688 −42.727 1.00 25.90 ATOM 4580 C2 MAN A 606−9.839 27.944 −41.452 1.00 28.64 ATOM 4581 O2 MAN A 606 −9.245 28.909−40.620 1.00 28.84 ATOM 4582 C3 MAN A 606 −10.999 27.249 −40.710 1.0029.65 ATOM 4583 O3 MAN A 606 −10.568 26.763 −39.441 1.00 28.85 ATOM 4584C4 MAN A 606 −12.203 28.177 −40.551 1.00 30.36 ATOM 4585 O4 MAN A 606−13.330 27.463 −40.084 1.00 30.29 ATOM 4586 CS MAN A 606 −12.553 28.769−41.914 1.00 30.72 ATOM 4587 C6 MAN A 606 −13.730 29.731 −41.778 1.0033.97 ATOM 4588 O6 MAN A 606 −13.624 30.732 −42.762 1.00 36.82 ATOM 4589O5 MAN A 606 −11.434 29.464 −42.435 1.00 28.12 ATOM 4590 C1 MAN A 607−31.396 1.963 −40.521 1.00 50.29 ATOM 4591 C2 MAN A 607 −30.220 1.790−41.485 1.00 52.65 ATOM 4592 O2 MAN A 607 −30.541 0.785 −42.419 1.0054.93 ATOM 4593 C3 MAN A 607 −29.845 3.092 −42.208 1.00 52.48 ATOM 4594O3 MAN A 607 −28.932 2.836 −43.251 1.00 53.01 ATOM 4595 C4 MAN A 607−31.068 3.818 −42.766 1.00 52.78 ATOM 4596 O4 MAN A 607 −30.672 5.070−43.297 1.00 52.92 ATOM 4597 C5 MAN A 607 −32.103 3.985 −41.652 1.0052.23 ATOM 4598 C6 MAN A 607 −33.331 4.749 −42.153 1.00 52.96 ATOM 4599O6 MAN A 607 −34.520 4.076 −41.791 1.00 52.95 ATOM 4600 O5 MAN A 607−32.451 2.702 −41.127 1.00 51.79 ATOM 4601 C1 MAN A 608 3.870 15.416−59.489 1.00 37.21 ATOM 4602 C2 MAN A 608 5.134 15.938 −60.168 1.0040.45 ATOM 4603 O2 MAN A 608 6.091 14.903 −60.120 1.00 38.47 ATOM 4604C3 MAN A 608 4.872 16.381 −61.608 1.00 42.66 ATOM 4605 O3 MAN A 6086.071 16.726 −62.263 1.00 44.20 ATOM 4606 C4 MAN A 608 4.122 15.321−62.401 1.00 44.80 ATOM 4607 O4 MAN A 608 3.708 15.907 −63.612 1.0047.73 ATOM 4608 C5 MAN A 608 2.893 14.887 −61.597 1.00 44.80 ATOM 4609C6 MAN A 608 2.042 13.861 −62.342 1.00 47.55 ATOM 4610 O6 MAN A 6081.085 14.582 −63.104 1.00 49.87 ATOM 4611 O5 MAN A 608 3.262 14.423−60.302 1.00 42.18 ATOM 4612 C1 NAG A 611 3.450 −2.354 −8.282 1.00 23.44ATOM 4613 C2 NAG A 611 3.474 −0.875 −7.878 1.00 24.51 ATOM 4614 N2 NAG A611 4.425 −0.077 −8.630 1.00 21.95 ATOM 4615 C7 NAG A 611 4.123 0.454−9.818 1.00 22.94 ATOM 4616 O7 NAG A 611 3.030 0.322 −10.367 1.00 20.93ATOM 4617 C8 NAG A 611 5.216 1.232 −10.481 1.00 21.54 ATOM 4618 C3 NAG A611 3.741 −0.713 −6.380 1.00 25.60 ATOM 4619 O3 NAG A 611 3.676 0.655−6.047 1.00 24.91 ATOM 4620 C4 NAG A 611 2.741 −1.528 −5.554 1.00 25.70ATOM 4621 O4 NAG A 611 3.196 −1.598 −4.227 1.00 28.27 ATOM 4622 C5 NAG A611 2.648 −2.952 −6.086 1.00 26.18 ATOM 4623 C6 NAG A 611 1.524 −3.738−5.397 1.00 26.64 ATOM 4624 O6 NAG A 611 0.278 −3.081 −5.497 1.00 25.38ATOM 4625 O5 NAG A 611 2.437 −2.975 −7.488 1.00 24.34 ATOM 4626 C1 NAG A612 2.499 −0.713 −3.326 1.00 32.04 ATOM 4627 C2 NAG A 612 2.710 −1.192−1.879 1.00 35.81 ATOM 4628 N2 NAG A 612 2.254 −2.556 −1.666 1.00 37.89ATOM 4629 C7 NAG A 612 3.072 −3.605 −1.753 1.00 39.19 ATOM 4630 O7 NAG A612 4.277 −3.517 −2.031 1.00 40.58 ATOM 4631 C8 NAG A 612 2.439 −4.947−1.507 1.00 38.98 ATOM 4632 C3 NAG A 612 2.012 −0.256 −0.899 1.00 37.96ATOM 4633 O3 NAG A 612 2.352 −0.666 0.403 1.00 41.23 ATOM 4634 C4 NAG A612 2.491 1.176 −1.129 1.00 37.63 ATOM 4635 O4 NAG A 612 1.789 2.053−0.278 1.00 40.85 ATOM 4636 C5 NAG A 612 2.294 1.565 −2.604 1.00 35.10ATOM 4637 C6 NAG A 612 2.785 2.982 −2.903 1.00 31.93 ATOM 4638 O6 NAG A612 4.188 2.994 −3.008 0.58 32.70 ATOM 4639 O5 NAG A 612 2.974 0.625−3.425 1.00 31.95 ATOM 4640 O8 BTB A 620 −1.213 18.638 −21.639 1.0023.78 ATOM 4641 C8 BTB A 620 −1.255 19.440 −22.838 1.00 17.50 ATOM 4642C7 BTB A 620 −2.257 18.851 −23.831 1.00 15.39 ATOM 4643 N BTB A 620−1.808 17.505 −24.294 1.00 13.88 ATOM 4644 C5 BTB A 620 −1.274 17.600−25.684 1.00 12.99 ATOM 4645 C6 BTB A 620 0.017 18.399 −25.786 1.0014.67 ATOM 4646 O6 BTB A 620 0.949 18.004 −24.768 1.00 16.93 ATOM 4647C2 BTB A 620 −2.926 16.495 −24.191 1.00 13.33 ATOM 4648 C4 BTB A 620−4.238 16.972 −24.835 1.00 13.45 ATOM 4649 O4 BTB A 620 −4.167 17.018−26.265 1.00 14.77 ATOM 4650 C3 BTB A 620 −3.213 16.295 −22.703 1.0013.18 ATOM 4651 O3 BTB A 620 −1.984 15.920 −22.059 1.00 12.74 ATOM 4652C1 BTB A 620 −2.501 15.161 −24.845 1.00 13.57 ATOM 4653 O1 BTB A 620−3.463 14.138 −24.525 1.00 13.07 ATOM 4654 O WAT W 1 −7.741 16.530−28.587 1.00 12.90 ATOM 4655 O WAT W 2 −1.955 18.721 −7.814 1.00 11.77ATOM 4656 O WAT W 3 −17.101 16.033 −19.836 1.00 15.26 ATOM 4657 O WAT W4 −1.389 7.464 −24.070 1.00 15.86 ATOM 4658 O WAT W 5 −8.070 20.758−43.462 1.00 19.56 ATOM 4659 O WAT W 6 −12.959 28.534 −26.860 1.00 16.12ATOM 4660 O WAT W 7 −0.502 31.488 −57.004 1.00 33.06 ATOM 4661 O WAT W 82.095 5.710 −17.808 1.00 18.68 ATOM 4662 O WAT W 9 −7.601 14.567 −6.8271.00 14.97 ATOM 4663 O WAT W 10 24.863 23.325 −37.431 1.00 32.31 ATOM4664 O WAT W 11 −22.569 7.289 −10.357 1.00 17.52 ATOM 4665 O WAT W 12−18.987 1.758 −22.078 1.00 23.03 ATOM 4666 O WAT W 13 −3.226 16.264−54.338 1.00 32.98 ATOM 4667 O WAT W 14 6.141 16.546 −42.196 1.00 16.00ATOM 4668 O WAT W 15 −10.356 21.827 −22.675 1.00 13.52 ATOM 4669 O WAT W16 −3.130 25.355 −17.925 1.00 14.01 ATOM 4670 O WAT W 17 −11.823 29.479−29.411 1.00 17.50 ATOM 4671 O WAT W 18 −14.383 15.964 −19.553 1.0013.02 ATOM 4672 O WAT W 19 −1.180 16.935 −10.101 1.00 18.86 ATOM 4673 OWAT W 20 −31.133 23.501 4.462 1.00 16.66 ATOM 4674 O WAT W 21 −4.81924.193 −15.023 1.00 14.31 ATOM 4675 O WAT W 22 1.709 22.276 −4.126 1.0021.96 ATOM 4676 O WAT W 23 −5.339 21.386 −7.463 1.00 15.78 ATOM 4677 OWAT W 24 −17.232 15.476 1.374 1.00 17.64 ATOM 4678 O WAT W 25 −11.4494.860 −24.929 1.00 17.45 ATOM 4679 O WAT W 26 −17.555 17.679 −39.8151.00 23.23 ATOM 4680 O WAT W 27 10.075 17.015 −49.295 1.00 24.05 ATOM4681 O WAT W 28 −16.018 −0.740 −24.205 1.00 18.07 ATOM 4682 O WAT W 299.446 24.991 −37.612 1.00 19.20 ATOM 4683 O WAT W 30 −4.165 26.137−12.642 1.00 18.33 ATOM 4684 O WAT W 31 2.771 22.947 −14.916 1.00 25.80ATOM 4685 O WAT W 32 −12.297 21.394 −35.680 1.00 14.89 ATOM 4686 O WAT W33 −24.061 13.570 10.081 1.00 24.96 ATOM 4687 O WAT W 34 10.032 29.725−56.684 1.00 26.97 ATOM 4688 O WAT W 35 0.231 4.133 −28.595 1.00 17.67ATOM 4689 O WAT W 36 0.335 2.173 −30.650 1.00 18.32 ATOM 4690 O WAT W 37−10.199 24.315 −42.717 1.00 22.38 ATOM 4691 O WAT W 38 −14.151 12.872−8.204 1.00 16.16 ATOM 4692 O WAT W 39 −2.710 9.564 −16.092 1.00 14.10ATOM 4693 O WAT W 40 5.954 7.990 −32.401 1.00 16.59 ATOM 4694 O WAT W 410.294 5.561 −25.249 1.00 17.87 ATOM 4695 O WAT W 42 2.102 15.148 −37.7181.00 14.64 ATOM 4696 O WAT W 43 −19.351 1.384 −26.295 1.00 20.27 ATOM4697 O WAT W 44 −19.623 9.533 −17.751 1.00 14.67 ATOM 4698 O WAT W 453.117 18.767 −36.336 1.00 12.66 ATOM 4699 O WAT W 46 −15.015 16.9500.662 1.00 20.14 ATOM 4700 O WAT W 47 −22.261 4.600 −10.993 1.00 16.38ATOM 4701 O WAT W 48 −12.926 5.474 −22.680 1.00 19.85 ATOM 4702 O WAT W49 5.564 17.071 −37.018 1.00 16.82 ATOM 4703 O WAT W 50 −19.848 20.552−2.718 1.00 19.38 ATOM 4704 O WAT W 51 −15.859 17.744 −41.901 1.00 19.69ATOM 4705 O WAT W 52 −16.430 25.522 −1.123 1.00 19.97 ATOM 4706 O WAT W53 −15.978 5.366 −12.193 1.00 26.02 ATOM 4707 O WAT W 54 −1.637 9.365−26.035 1.00 14.42 ATOM 4708 O WAT W 55 −10.759 27.212 −30.898 1.0017.28 ATOM 4709 O WAT W 56 −11.509 0.756 −13.101 1.00 20.70 ATOM 4710 OWAT W 57 −16.950 15.108 4.727 1.00 23.86 ATOM 4711 O WAT W 58 −25.36826.009 −7.106 1.00 25.08 ATOM 4712 O WAT W 59 −16.870 22.937 −3.651 1.0017.56 ATOM 4713 O WAT W 60 −14.388 13.258 −40.897 1.00 27.90 ATOM 4714 OWAT W 61 −1.509 −4.779 −6.723 1.00 31.01 ATOM 4715 O WAT W 62 −1.97327.723 −11.521 1.00 21.99 ATOM 4716 O WAT W 63 −1.159 −10.623 −29.5921.00 36.68 ATOM 4717 O WAT W 64 −1.943 16.930 −42.957 1.00 21.57 ATOM4718 O WAT W 65 −1.507 25.238 −40.032 1.00 31.36 ATOM 4719 O WAT W 66−4.023 5.499 −31.787 1.00 20.03 ATOM 4720 O WAT W 67 −13.383 13.873−21.065 1.00 12.01 ATOM 4721 O WAT W 68 −15.098 10.726 −24.467 1.0024.34 ATOM 4722 O WAT W 69 −2.122 13.975 −13.435 1.00 12.51 ATOM 4723 OWAT W 70 −4.607 19.360 −43.270 1.00 20.93 ATOM 4724 O WAT W 71 −26.02826.143 −33.768 1.00 28.73 ATOM 4725 O WAT W 72 −19.347 21.638 3.482 1.0019.92 ATOM 4726 O WAT W 73 −27.299 24.219 −6.045 1.00 20.97 ATOM 4727 OWAT W 74 −21.114 −0.343 −28.050 1.00 22.38 ATOM 4728 O WAT W 75 −5.81834.483 −11.645 1.00 20.61 ATOM 4729 O WAT W 76 6.048 1.098 −23.393 1.0016.77 ATOM 4730 O WAT W 77 −3.946 23.711 −39.552 1.00 25.07 ATOM 4731 OWAT W 78 −18.572 21.631 −41.884 1.00 25.98 ATOM 4732 O WAT W 79 5.23926.273 −31.646 1.00 27.95 ATOM 4733 O WAT W 80 0.054 15.597 −45.905 1.0028.45 ATOM 4734 O WAT W 81 −3.130 21.534 −5.652 1.00 20.95 ATOM 4735 OWAT W 82 −12.534 4.331 −20.095 1.00 17.49 ATOM 4736 O WAT W 83 0.78516.541 −14.558 1.00 14.65 ATOM 4737 O WAT W 84 −5.197 12.827 −31.5531.00 14.10 ATOM 4738 O WAT W 85 −16.738 26.994 −34.463 1.00 23.74 ATOM4739 O WAT W 86 3.596 22.076 −36.828 1.00 22.68 ATOM 4740 O WAT W 875.170 14.460 −40.572 1.00 26.56 ATOM 4741 O WAT W 88 −12.322 21.0500.328 1.00 30.36 ATOM 4742 O WAT W 89 7.426 14.327 −48.857 1.00 26.44ATOM 4743 O WAT W 90 −13.702 19.025 1.863 1.00 28.28 ATOM 4744 O WAT W91 8.794 2.010 −23.444 1.00 34.69 ATOM 4745 O WAT W 92 −6.185 5.529−30.210 1.00 17.03 ATOM 4746 O WAT W 93 −18.081 20.709 −4.839 1.00 17.61ATOM 4747 O WAT W 94 −15.469 13.082 −22.717 1.00 15.55 ATOM 4748 O WAT W95 13.101 16.811 −29.771 1.00 29.16 ATOM 4749 O WAT W 96 −25.944 7.031−2.628 1.00 27.42 ATOM 4750 O WAT W 97 −4.552 34.207 −7.388 1.00 22.19ATOM 4751 O WAT W 98 −2.231 −9.858 −32.291 1.00 26.28 ATOM 4752 O WAT W99 5.314 10.271 −28.762 1.00 29.39 ATOM 4753 O WAT W 100 −15.379 27.478−46.620 1.00 37.77 ATOM 4754 O WAT W 101 26.815 24.874 −36.295 1.0031.11 ATOM 4755 O WAT W 102 −18.489 −0.112 −24.256 1.00 23.63 ATOM 4756O WAT W 103 −23.763 26.890 −9.454 1.00 20.50 ATOM 4757 O WAT W 104−10.933 23.904 −50.315 1.00 25.63 ATOM 4758 O WAT W 105 5.864 12.071−41.668 1.00 29.27 ATOM 4759 O WAT W 106 2.526 9.409 −13.116 1.00 20.75ATOM 4760 O WAT W 107 −11.557 −6.653 −10.981 1.00 30.68 ATOM 4761 O WATW 108 −14.882 7.238 −22.254 1.00 24.81 ATOM 4762 O WAT W 109 −5.331−13.390 −25.293 1.00 35.63 ATOM 4763 O WAT W 110 −8.068 24.248 −40.5341.00 39.14 ATOM 4764 O WAT W 111 −0.779 14.419 −43.060 1.00 24.01 ATOM4765 O WAT W 112 −22.279 12.054 −26.750 1.00 32.13 ATOM 4766 O WAT W 113−26.829 1.352 −33.787 1.00 26.97 ATOM 4767 O WAT W 114 −14.120 14.1163.214 1.00 36.89 ATOM 4768 O WAT W 115 0.582 −9.914 −21.103 1.00 23.30ATOM 4769 O WAT W 116 −24.305 22.723 6.995 1.00 21.67 ATOM 4770 O WAT W117 −28.275 12.468 −15.419 1.00 21.87 ATOM 4771 O WAT W 118 3.699 27.669−20.781 1.00 34.08 ATOM 4772 O WAT W 119 −30.428 26.452 3.757 1.00 24.51ATOM 4773 O WAT W 120 19.168 26.858 −59.022 1.00 33.45 ATOM 4774 O WAT W121 −8.803 21.729 −1.693 1.00 18.30 ATOM 4775 O WAT W 122 2.863 1.621−31.755 1.00 19.96 ATOM 4776 O WAT W 123 −2.357 28.930 −56.725 1.0035.51 ATOM 4777 O WAT W 124 −16.780 5.504 −21.523 1.00 31.34 ATOM 4778 OWAT W 125 6.216 18.141 −30.592 1.00 20.87 ATOM 4779 O WAT W 126 11.78932.722 −38.773 1.00 40.41 ATOM 4780 O WAT W 127 −5.001 7.195 −45.6561.00 35.03 ATOM 4781 O WAT W 128 −18.743 1.608 −1.861 1.00 32.49 ATOM4782 O WAT W 129 −25.089 −1.945 −20.935 1.00 35.17 ATOM 4783 O WAT W 130−7.097 −2.177 −28.928 1.00 30.93 ATOM 4784 O WAT W 131 −12.591 2.907−11.929 1.00 18.60 ATOM 4785 O WAT W 132 −17.913 −2.374 −39.429 1.0029.36 ATOM 4786 O WAT W 133 −6.507 −7.038 −37.710 1.00 37.27 ATOM 4787 OWAT W 134 −0.628 7.596 −18.660 1.00 20.01 ATOM 4788 O WAT W 135 −11.68328.527 −37.016 1.00 36.45 ATOM 4789 O WAT W 136 −3.169 33.267 −18.0491.00 24.89 ATOM 4790 O WAT W 137 −16.742 8.938 −23.161 1.00 26.79 ATOM4791 O WAT W 138 −28.456 17.726 −22.449 1.00 32.61 ATOM 4792 O WAT W 13925.559 27.237 −45.392 1.00 43.21 ATOM 4793 O WAT W 140 −26.925 5.789−41.722 1.00 26.97 ATOM 4794 O WAT W 141 −16.907 20.013 −43.283 1.0029.68 ATOM 4795 O WAT W 142 −20.029 5.119 −1.799 1.00 24.76 ATOM 4796 OWAT W 143 8.706 1.050 −13.115 1.00 32.81 ATOM 4797 O WAT W 144 −4.35322.506 −1.252 1.00 24.86 ATOM 4798 O WAT W 145 −29.660 14.750 −15.2951.00 32.62 ATOM 4799 O WAT W 146 2.173 2.240 −12.124 1.00 26.38 ATOM4800 O WAT W 147 4.174 −4.659 −14.794 1.00 25.20 ATOM 4801 O WAT W 148−10.913 29.083 −33.130 1.00 27.78 ATOM 4802 O WAT W 149 −21.448 30.157−10.670 1.00 25.07 ATOM 4803 O WAT W 150 −23.296 18.641 −36.646 1.0027.11 ATOM 4804 O WAT W 151 −19.426 8.262 −24.240 1.00 25.11 ATOM 4805 OWAT W 152 4.729 −0.512 −31.679 1.00 23.50 ATOM 4806 O WAT W 153 9.24719.703 −33.306 1.00 23.44 ATOM 4807 O WAT W 154 6.024 15.401 −22.7681.00 27.11 ATOM 4808 O WAT W 155 −16.077 30.180 −4.530 1.00 23.52 ATOM4809 O WAT W 156 −0.038 14.751 −8.812 1.00 25.64 ATOM 4810 O WAT W 1572.962 18.631 −29.190 1.00 18.13 ATOM 4811 O WAT W 158 8.793 12.371−36.745 1.00 23.77 ATOM 4812 O WAT W 159 −22.406 9.468 −0.415 1.00 21.66ATOM 4813 O WAT W 160 −10.961 33.685 −7.076 1.00 25.30 ATOM 4814 O WAT W161 −8.504 27.891 −3.964 1.00 33.88 ATOM 4815 O WAT W 162 6.836 20.663−32.439 1.00 24.97 ATOM 4816 O WAT W 163 4.292 23.232 −29.206 1.00 32.74ATOM 4817 O WAT W 164 2.350 3.656 −15.645 1.00 23.29 ATOM 4818 O WAT W165 −17.377 10.190 −20.605 1.00 25.21 ATOM 4819 O WAT W 166 −23.42624.714 4.551 1.00 26.12 ATOM 4820 O WAT W 167 0.338 1.730 −14.995 1.0031.29 ATOM 4821 O WAT W 168 −3.303 17.836 −46.350 1.00 28.34 ATOM 4822 OWAT W 169 1.465 6.514 −14.840 1.00 22.81 ATOM 4823 O WAT W 170 2.40911.466 −4.481 1.00 29.82 ATOM 4824 O WAT W 171 0.998 19.313 −20.348 1.0031.57 ATOM 4825 O WAT W 172 7.556 −3.076 −34.213 1.00 31.62 ATOM 4826 OWAT W 173 −25.163 1.132 −18.852 1.00 33.45 ATOM 4827 O WAT W 174 −25.60617.471 −26.509 1.00 27.89 ATOM 4828 O WAT W 175 5.952 32.621 −65.9551.00 42.20 ATOM 4829 O WAT W 176 −27.397 26.421 −12.489 1.00 29.06 ATOM4830 O WAT W 177 −17.506 35.918 −29.284 1.00 36.40 ATOM 4831 O WAT W 178−18.298 7.055 −19.628 1.00 30.04 ATOM 4832 O WAT W 179 −24.383 14.811−26.605 1.00 29.51 ATOM 4833 O WAT W 180 −1.204 27.462 −35.328 1.0029.93 ATOM 4834 O WAT W 181 −14.112 33.822 −23.916 1.00 34.66 ATOM 4835O WAT W 182 2.887 26.714 −9.619 1.00 34.18 ATOM 4836 O WAT W 183 −16.0624.698 1.046 1.00 32.44 ATOM 4837 O WAT W 184 −13.340 36.111 −4.359 1.0039.14 ATOM 4838 O WAT W 185 9.661 34.457 −47.977 1.00 37.66 ATOM 4839 OWAT W 186 −8.465 24.284 −1.237 1.00 33.71 ATOM 4840 O WAT W 187 16.97115.520 −43.951 1.00 42.49 ATOM 4841 O WAT W 188 −12.038 −14.614 −20.2991.00 34.37 ATOM 4842 O WAT W 189 −5.887 22.387 −40.784 1.00 33.70 ATOM4843 O WAT W 190 −3.962 −18.100 −17.720 1.00 31.33 ATOM 4844 O WAT W 191−30.888 11.643 −15.288 1.00 36.84 ATOM 4845 O WAT W 192 11.576 13.142−37.752 1.00 32.89 ATOM 4846 O WAT W 193 −7.856 3.348 −41.927 1.00 34.02ATOM 4847 O WAT W 194 −20.849 7.518 7.652 1.00 32.37 ATOM 4848 O WAT W195 16.954 13.938 −58.514 1.00 42.65 ATOM 4849 O WAT W 196 −31.884 7.593−13.893 1.00 37.54 ATOM 4850 O WAT W 197 4.560 −14.190 −17.137 1.0036.09 ATOM 4851 O WAT W 198 1.116 27.617 −39.051 1.00 37.08 ATOM 4852 OWAT W 199 −1.019 −12.134 −21.800 1.00 36.12 ATOM 4853 O WAT W 200 8.3500.111 −21.198 1.00 36.56 ATOM 4854 O WAT W 201 −2.691 31.235 −26.9101.00 32.08 ATOM 4855 O WAT W 202 13.222 30.530 −38.626 1.00 36.46 ATOM4856 O WAT W 203 −11.218 19.535 −54.549 1.00 35.12 ATOM 4857 O WAT W 204−5.623 10.865 −46.910 1.00 35.48 ATOM 4858 O WAT W 205 −18.073 1.743−43.946 1.00 40.62 ATOM 4859 O WAT W 206 −32.195 23.231 2.102 1.00 34.73ATOM 4860 O WAT W 207 −24.204 8.994 −2.941 1.00 30.29 ATOM 4861 O WAT W208 −4.771 18.292 −48.610 1.00 31.87 ATOM 4862 O WAT W 209 −17.15623.843 −40.674 1.00 35.73 ATOM 4863 O WAT W 210 8.319 13.422 −13.2971.00 37.43 ATOM 4864 O WAT W 211 −25.962 8.559 −33.791 1.00 33.46 ATOM4865 O WAT W 212 −36.129 8.276 3.147 1.00 40.24 ATOM 4866 O WAT W 21320.833 21.074 −56.185 1.00 39.11 ATOM 4867 O WAT W 214 −17.726 14.0878.330 1.00 39.10 ATOM 4868 O WAT W 215 8.944 8.011 −10.493 1.00 41.24ATOM 4869 O WAT W 216 −16.566 35.858 −11.282 1.00 38.90 ATOM 4870 O WATW 217 −20.560 11.198 −43.128 1.00 34.83 ATOM 4871 O WAT W 218 3.261−0.833 −39.177 1.00 32.67 ATOM 4872 O WAT W 219 −22.370 −13.152 −34.4121.00 59.42 ATOM 4873 O WAT W 220 −24.775 6.925 5.968 1.00 34.28 ATOM4874 O WAT W 221 −20.357 21.098 −45.702 1.00 36.83 ATOM 4875 O WAT W 2222.502 28.932 −40.686 1.00 36.85 ATOM 4876 O WAT W 223 −17.630 −5.533−21.334 1.00 35.08 ATOM 4877 O WAT W 224 −19.358 −1.912 −43.190 1.0035.83 ATOM 4878 O WAT W 225 −14.632 25.995 −42.094 1.00 41.12 ATOM 4879O WAT W 226 −28.967 5.606 −22.103 1.00 45.63 ATOM 4880 O WAT W 227−4.326 9.934 5.097 1.00 44.46 ATOM 4881 O WAT W 228 3.983 22.711 −17.3361.00 46.21 ATOM 4882 O WAT W 229 −17.238 16.931 6.949 1.00 42.44 ATOM4883 O WAT W 230 −25.871 18.809 10.364 1.00 36.15 ATOM 4884 O WAT W 231−23.524 31.294 −19.082 1.00 35.99 ATOM 4885 O WAT W 232 −5.261 −9.321−38.277 1.00 43.42 ATOM 4886 O WAT W 233 −22.757 28.188 −29.173 1.0039.56 ATOM 4887 O WAT W 234 −25.699 26.238 −0.299 1.00 40.26 ATOM 4888 OWAT W 235 −21.884 −4.007 −22.294 1.00 38.01 ATOM 4889 O WAT W 236 −6.696−17.346 −27.753 1.00 39.83 ATOM 4890 O WAT W 237 −18.052 5.515 3.8881.00 37.82 ATOM 4891 O WAT W 238 −6.073 35.708 −9.057 1.00 36.25 ATOM4892 O WAT W 239 −8.876 2.984 −44.368 1.00 45.85 ATOM 4893 O WAT W 2409.232 31.613 −65.496 1.00 45.82 ATOM 4894 O WAT W 241 −28.246 26.806−0.118 1.00 36.45 ATOM 4895 O WAT W 242 −27.793 14.675 −45.312 1.0052.10 ATOM 4896 O WAT W 243 7.463 14.079 −55.045 1.00 36.97 ATOM 4897 OWAT W 244 −28.572 4.769 −1.130 1.00 36.20 ATOM 4898 O WAT W 245 8.22112.936 −50.870 1.00 38.81 ATOM 4899 O WAT W 246 −23.302 −2.082 −27.1911.00 32.98 ATOM 4900 O WAT W 247 −13.035 8.248 −46.620 1.00 51.73 ATOM4901 O WAT W 248 −11.869 31.852 −50.157 1.00 56.13 ATOM 4902 O WAT W 2490.898 13.920 −6.521 1.00 27.38 ATOM 4903 O WAT W 250 20.427 30.852−45.446 1.00 35.54 ATOM 4904 O WAT W 251 −1.397 12.400 −44.617 1.0039.33 ATOM 4905 O WAT W 252 −27.354 24.696 −3.162 1.00 35.38 ATOM 4906 OWAT W 253 17.587 20.557 −31.069 1.00 41.51 ATOM 4907 O WAT W 254 −7.93635.055 −7.354 1.00 39.02 ATOM 4908 O WAT W 255 −22.469 7.215 −2.044 1.0038.25 ATOM 4909 O WAT W 256 2.038 15.474 −52.963 1.00 50.04 ATOM 4910 OWAT W 257 10.889 10.184 −21.700 1.00 44.84 ATOM 4911 O WAT W 258 −11.71410.583 4.136 1.00 42.70 ATOM 4912 O WAT W 259 −14.719 6.574 2.959 1.0043.18 ATOM 4913 O WAT W 260 −16.694 25.390 −37.688 1.00 36.77 ATOM 4914O WAT W 261 −9.212 13.388 −48.363 1.00 38.05 ATOM 4915 O WAT W 264−0.611 −1.965 −3.253 1.00 37.95 ATOM 4916 O WAT W 265 −16.380 30.998−14.262 1.00 32.44 ATOM 4917 O WAT W 266 9.420 16.012 −61.368 1.00 35.22ATOM 4918 O WAT W 267 −4.976 −15.180 −21.223 1.00 45.50 ATOM 4919 O WATW 268 −16.631 33.287 −14.201 1.00 34.50 ATOM 4920 O WAT W 269 −16.88334.052 −32.249 1.00 36.88 ATOM 4921 O WAT W 270 −8.293 −16.006 −14.5351.00 34.80 ATOM 4922 O WAT W 273 0.240 4.589 −13.868 1.00 32.34 ATOM4923 O WAT W 275 3.657 14.447 −55.516 1.00 43.54 ATOM 4924 O WAT W 276−17.602 20.784 −51.471 1.00 38.88 ATOM 4925 O WAT W 277 −10.479 31.683−30.513 1.00 40.35 ATOM 4926 O WAT W 278 −10.974 4.308 −5.745 1.00 40.30ATOM 4927 O WAT W 280 −4.336 36.908 −17.666 1.00 34.01 ATOM 4928 O WAT W281 6.720 33.970 −53.572 1.00 38.81 ATOM 4929 O WAT W 282 −30.457 23.527−0.621 1.00 34.61 ATOM 4930 O WAT W 283 16.969 17.394 −30.816 1.00 55.74ATOM 4931 O WAT W 284 −24.391 5.834 −24.909 1.00 37.92 ATOM 4932 O WAT W285 4.567 9.814 −4.438 1.00 44.83 ATOM 4933 O WAT W 286 −24.370 −7.328−27.875 1.00 56.18 ATOM 4934 O WAT W 287 −21.605 11.887 9.715 1.00 43.15ATOM 4935 O WAT W 288 8.603 0.412 −37.887 1.00 40.47 ATOM 4936 O WAT W290 −20.056 21.495 6.073 1.00 41.68 ATOM 4937 O WAT W 291 −3.221 28.158−33.448 1.00 44.24 ATOM 4938 O WAT W 292 9.171 9.103 −38.735 1.00 34.30ATOM 4939 O WAT W 293 2.894 22.763 −25.829 1.00 38.57 ATOM 4940 O WAT W294 −29.901 19.604 −14.929 1.00 37.66 ATOM 4941 O WAT W 296 −4.57930.229 −29.110 1.00 40.57 ATOM 4942 O WAT W 297 −23.821 11.441 −33.1871.00 42.81 ATOM 4943 O WAT W 298 −26.753 −3.087 −31.243 1.00 39.08 ATOM4944 O WAT W 300 −10.820 35.024 −53.050 1.00 55.39 ATOM 4945 O WAT W 302−1.992 7.169 −31.692 1.00 39.12 ATOM 4946 O WAT W 303 −15.282 −19.000−23.770 1.00 34.62 ATOM 4947 O WAT W 304 12.106 10.568 −25.112 1.0039.04 ATOM 4948 O WAT W 305 2.585 2.766 1.880 1.00 53.88 ATOM 4949 O WATW 306 3.680 21.122 −19.810 1.00 46.35 ATOM 4950 O WAT W 307 22.75924.721 −48.099 1.00 40.35 ATOM 4951 O WAT W 309 −17.062 −6.726 −19.2021.00 41.54 ATOM 4952 O WAT W 311 12.594 1.109 −31.461 1.00 47.85 ATOM4953 O WAT W 312 23.347 25.060 −50.638 1.00 49.64 ATOM 4954 O WAT W 314−18.291 4.422 −19.151 1.00 39.17 ATOM 4955 O WAT W 315 −11.815 −7.807−8.676 1.00 37.74 ATOM 4956 O WAT W 316 −25.147 1.885 −4.649 1.00 44.72ATOM 4957 O WAT W 317 −36.473 13.592 5.315 1.00 44.38 ATOM 4958 O WAT W318 −17.587 20.023 −46.231 1.00 48.30 ATOM 4959 O WAT W 319 −16.08129.024 −54.668 1.00 39.40 ATOM 4960 O WAT W 320 −14.210 32.143 −5.4941.00 42.73 ATOM 4961 O WAT W 321 −15.274 28.830 −38.916 1.00 46.47 ATOM4962 O WAT W 322 −32.792 22.221 −3.433 1.00 41.52 ATOM 4963 O WAT W 323−32.475 16.905 −12.401 1.00 46.29 ATOM 4964 O WAT W 325 15.341 22.212−60.490 1.00 34.67 ATOM 4965 O WAT W 326 −12.668 8.518 −41.723 1.0036.26 ATOM 4966 O WAT W 327 4.709 20.490 −10.568 1.00 38.04 ATOM 4967 OWAT W 328 13.937 10.625 −29.312 1.00 38.32 ATOM 4968 O WAT W 329 −21.9649.615 −24.896 1.00 40.43 ATOM 4969 O WAT W 330 19.325 25.925 −40.1991.00 51.36 ATOM 4970 O WAT W 331 −19.010 8.073 −45.255 1.00 46.06 ATOM4971 O WAT W 332 −25.024 −2.892 −29.306 1.00 41.74 ATOM 4972 O WAT W 333−16.593 −7.067 −23.297 1.00 38.54 ATOM 4973 O WAT W 334 −17.517 24.0782.157 1.00 45.82 ATOM 4974 O WAT W 335 −19.123 31.941 0.010 1.00 38.91ATOM 4975 O WAT W 337 10.677 21.901 −62.740 1.00 44.31 ATOM 4976 O WAT W338 4.510 15.230 −51.810 1.00 42.12 ATOM 4977 O WAT W 339 13.979 14.161−43.380 1.00 46.42 ATOM 4978 O WAT W 341 5.979 −11.625 −28.739 1.0043.09 ATOM 4979 O WAT W 342 −19.453 13.347 10.394 1.00 42.44 ATOM 4980 OWAT W 343 7.085 23.050 −30.796 1.00 34.94 ATOM 4981 O WAT W 345 6.47124.087 −63.943 1.00 45.16 ATOM 4982 O WAT W 347 3.734 22.842 −12.0311.00 43.85 ATOM 4983 O WAT W 348 −17.739 7.564 5.723 1.00 43.77 ATOM4984 O WAT W 351 −22.014 31.372 −24.708 1.00 42.69 ATOM 4985 O WAT W 35225.016 25.103 −46.967 1.00 40.51 ATOM 4986 O WAT W 353 7.969 32.464−67.637 1.00 57.78 ATOM 4987 O WAT W 354 −27.444 5.101 5.861 1.00 48.31ATOM 4988 O WAT W 356 8.012 11.087 −40.867 1.00 47.51 ATOM 4989 O WAT W357 4.974 29.116 −17.433 1.00 43.72 ATOM 4990 O WAT W 358 −0.457 9.488−45.288 1.00 45.63 ATOM 4991 O WAT W 360 −3.090 36.536 −12.138 1.0046.29 ATOM 4992 O WAT W 361 20.072 19.772 −36.896 1.00 38.73 ATOM 4993 OWAT W 363 −26.217 15.345 −28.735 1.00 49.07 ATOM 4994 O WAT W 365−25.308 0.100 −48.602 1.00 60.01 ATOM 4995 O WAT W 367 19.369 29.586−58.438 1.00 48.19 ATOM 4996 O WAT W 369 12.806 11.144 −54.427 1.0048.48 ATOM 4997 O WAT W 370 9.410 2.674 −16.115 1.00 44.59 ATOM 4998 OWAT W 372 −10.249 38.564 −13.215 1.00 48.60 ATOM 4999 O WAT W 373−24.151 16.211 10.617 1.00 42.16 ATOM 5000 O WAT W 375 −6.459 31.697−48.106 1.00 46.03 ATOM 5001 O WAT W 376 −11.605 27.116 −1.562 1.0044.58 ATOM 5002 O WAT W 377 −4.703 24.150 −62.673 1.00 48.70 ATOM 5003 OWAT W 379 6.889 0.036 −7.530 1.00 45.35 ATOM 5004 O WAT W 381 −13.60132.742 −32.002 1.00 51.37 ATOM 5005 O WAT W 383 −28.077 5.243 −4.6881.00 37.46

1-22. (canceled)
 23. An isolated glucoamylase variant comprising acatalytic domain and a starch binding domain (SBD), a) said catalyticdomain comprising at least 85% sequence identity to the amino acidsequence of SEQ ID NO:3 and b) said SBD comprising one or more aminoacid substitutions at a position corresponding to position: 3, 4, 5, 11,12, 13, 18, 21, 27, 28, 29, 30, 35, 37, 41, 43, 45, 46, 47, 48, 49, 50,55, 56, 57, 59, 61, 71, 73, 77, 79, 87, 89, and 93 of SEQ ID NO: 11 orsaid SBD comprising one or more amino acid substitutions in anequivalent position to SEQ ID NO: 11 of a parent glucoamylase SBD;wherein the equivalent position in a parent glucoamylase is determinedby sequence identity and said parent glucoamylase has at least 80% aminoacid sequence identity and less than 100% amino acid sequence identitywith SEQ ID NO:
 11. 24. The isolated glucoamylase variant of claim 23,wherein the catalytic domain has at least 90% sequence identity to theamino acid sequence of SEQ ID NO:3.
 25. The isolated glucoamylasevariant of claim 23, wherein the catalytic domain has at least 95%sequence identity to the amino acid sequence of SEQ ID NO:3.
 26. Theisolated glucoamylase variant of claim 23, wherein said SBD comprisesone or more amino acid substitutions at a position corresponding toposition: 3, 4, 5, 11, 12, 13, 18, 21, 27, 28, 29, 30, 35, 37, 41, 43,45, 46, 47, 48, 49, 50, 55, 56, 57, 59, 61, 71, 73, 77, 79, 87, 89, and93 of SEQ ID NO:
 11. 27. The glucoamylase variant of claim 23, whereinthe SBD comprises one or more amino acid substitutions corresponding topositions 3, 4, 5, 12, 13, 18, 21, 28, 29, 30, 37, 41, 45, 46, 47, 49,73, and 87 of SEQ ID NO: 11 or an equivalent position of a SBD of aparent glucoamylase.
 28. The glucoamylase variant of claim 23, whereinthe one or more amino acid substitutions corresponds to a positionchosen from positions 3, 5, 13, 18, 21, 28, 29, 30, 37, 41, 45, 46, 47,49, 73, and 87 of SEQ ID NO:
 11. 29. The glucoamylase variant of claim28, wherein the one or more amino acid substitutions corresponds to aposition chosen from positions 5, 13, 21, 30, 41, 45, 46, and 49 of SEQID NO:
 11. 30. The isolated glucoamylase variant of claim 23, whereinthe variant has at least one altered property as compared to the parentglucoamylase.
 31. The isolated glucoamylase variant of claim 30, whereinthe altered property is an increase in specific activity, an increase inthermostability or both. 32-34. (canceled)
 35. A polynucleotide encodingthe variant of claim
 23. 36. A host cell comprising the polynucleotideof claim
 35. 37. An enzyme composition comprising the glucoamylasevariant of claim
 23. 38. The enzyme composition of claim 37, whereinsaid composition is used in a starch conversion process.
 39. The enzymecomposition of claim 38, wherein said composition further comprises analpha amylase.
 40. The enzyme composition of claim 37, wherein saidcomposition is used in an animal feed formulation.
 41. The enzymecomposition of claim 37, wherein said composition is used in an alcoholfermentation process.
 42. A method of producing a variant glucoamylasein a host cell comprising transforming a host cell with a DNA constructcomprising a polynucleotide of claim 35; culturing the host cell underconditions suitable for the expression and production of saidglucoamylase variant and producing said variant.
 43. The methodaccording to claim 42 further comprising recovering the glucoamylasevariant from said culture.